Meibomian gland illuminating and imaging

ABSTRACT

In an illustrative embodiment, an apparatus for imaging a portion of a mammalian eyelid has an eye contact lenspiece configured to direct the light through an eyelid from posterior to anterior surface to thereby trans-illuminate the eyelid, when the light source illuminates the contact lens. An imaging device receives an image of the eyelid as it is trans-illuminated. Other methods and apparatus are presented in various embodiments, hence this abstract is not to be considered limiting, since other embodiments may deviate from the features described in this abstract.

RELATED APPLICATIONS

The present application is a divisional application of U.S. patentapplication Ser. No. 11/893,699 filed Aug. 17, 2007, entitled “MeibomianGland Illuminating and Imaging,” which is a continuation-in-part of, andclaims priority to, U.S. patent application Ser. No. 11/540,422 filedSep. 29, 2006, entitled “Meibomian Gland Imaging,” and is furtherrelated to, and claims priority to, U.S. Provisional Patent ApplicationNo. 60/880,850 filed Jan. 17, 2007, entitled “Method and Apparatus forTreating Meibomian Gland Obstructive Disease,” all of which areincorporated herein by reference in their entireties.

FIELD

This invention relates generally to the field of illuminating andimaging of eyelids of mammals. In particular, certain embodimentsconsistent with the invention relate to imaging of mammalian meibomianglands (also known as tarsal glands) or other structures orabnormalities of the eyelid including imaging of the meibomian glands todetermine a degree of secretory function, dysfunction obstruction, fullor partial obstruction, occlusion, dropout, diagnosis or effectivenessof treatment of such glands.

BACKGROUND

The human body contains a number of glands including the lacrimal andmeibomian glands of the eye, the sebaceous or pilo-sebaceous hair glandson the face and underarms, and the mammary glands in the breasts. Theseglands may malfunction due to age, irritation, environmental conditions,cellular debris, inflammation, hormonal imbalance and other causes. Onecommon disease state of the eyelid glands is the restriction or stoppageof the natural flow of fluid out of the gland caused by an obstruction.

In the human eye, the tear film covering the ocular surfaces is composedof three layers. The innermost layer in contact with the ocular surfaceis the mucus layer comprised of many mucins. The middle layer comprisingthe bulk of the tear film is the aqueous layer, and the outermost layeris a thin (less than 250 nm) layer comprised of many lipids known as“meibum” or “sebum”. The sebum is secreted by the meibomian glands,enlarged specialized sebaceous-type glands (hence, the use of “sebum” todescribe the secretion) located on both the upper and lower eye lids,with orifices designed to discharge the lipid secretions onto the lidmargins, thus forming the lipid layer of the tear film. The typicalupper eyelid has about 25-30 meibomian glands, and the lower eyelid hasabout 20-25 meibomian glands, which are somewhat larger than thoselocated in the upper lid. The precise number varies with eachindividual. The meibomian gland is comprised of various sac-like aciniwhich discharge the secretion into the main central duct of the gland.The secretion is then discharged through the orifice onto the lidmargin. The duct is surrounded by smooth muscle tissue and the muscle ofRiolan, whose contraction is presumed to aid in the expression of sebum.The meibomian gland orifices open onto the lid margin at and around thejunction of the inner mucous membrane and the outer skin of the eyelidstermed the mucocutaneous junction.

Specifically, each meibomian gland has a straight long central ductlined with four epithelial layers on the inner surface of the duct. Atthe opening of the duct, the four layers increase to six with theselayers containing more keratin than the layers further from the glandorifice

Along the length of the central duct there are multiple lateralout-pouching structures, termed acini where the secretion of the glandis manufactured. The inner lining of each acinus differs from the maincentral duct in that these specialized cells provide the secretions ofthe meibomian gland. The secretions flow from each acinus to the duct.While it has not been established with certainty, there appears to be avalve system between each acinus and the central duct to retain thesecretion until it is required, at which time it is discharged in to thecentral duct. The meibomian secretion is then stored in the central ductand is released through the orifice of each gland onto the lid margin.Blinking and the squeezing action of the muscle of Riolan surroundingthe meibomian glands are thought to be the primary mechanism to open theorifice for the release of secretion from the meibomian gland.

Blinking causes the upper lid to pull a sheet of the lipids secreted bythe meibomian glands over the other two layers of the tear film, thusforming a type of protective coating which limits the rate at which theunderlying layers evaporate. When the lipid layer is pulled up by theblink, the aqueous layer may also be pulled up since the lipid layerutilizes a form of attachment to the aqueous layer with specializedinterfacial molecules. When this occurs the lipid layer is readilyvisualized with interferometry, however, the movement of the aqueouslayer, particularly regarding its correlation to then lipid layer cannotbe observed. Thus, it will be seen that a defective lipid layer or anincorrect quantity of such lipids can result in accelerated evaporationof the aqueous layer which, in turn, causes symptoms such as itchiness,burning, irritation, and dryness, which symptoms suggest a condition orstate of “dry eye”.

Dry eye states have many etiologies. A common cause of common dry eyestates is a disorder where the glands are obstructed or occluded,usually referred to as “meibomian gland dysfunction” (MGD). As employedherein the terms “occluded” and “obstruction” as they relate tomeibomian gland dysfunction are defined as partially or completelyblocked or plugged meibomian glands, or any component thereof, having asolid, semi-solid or thickened congealed secretion and/or plug, leadingto a compromise, or more specifically, a decrease or cessation ofsecretion. Also with a reduced or limited secretion the meibomian glandmay be compromised by the occluded or obstructive condition as evidencedby a yellowish color indicating a possible infective state, or may beotherwise compromised so that the resulting lipid protective film of thetear layer is not adequate.

Meibomitis, an inflammation of the meibomian glands leading to theirdysfunction, is usually accompanied by blepharitis (inflammation of thelids). Meibomian gland dysfunction may accompany meibomitis, ormeibomian gland dysfunction may be present without obvious lidinflammation. Meibomian gland dysfunction is frequently the result ofkeratotic obstructions which partially or completely block the meibomiangland orifices and/or the central duct (canal) of the gland, or possiblythe acini or acini valves (assuming they do in fact exist) or theacini's junction with the central duct. Such obstructions compromise thesecretory functions of the individual meibomian glands. Moreparticularly, these keratotic obstructions can comprise combination ofbacteria, sebaceous ground substance, dead, and/or desquamatedepithelial cells, see, Korb et al., Meibomian Gland Dysfunction andContact Lens Intolerance, Journal of the Optometric Association, Vol.51, Number 3, (1980), pp. 243-251. While meibomitis is obvious byinspection of the external lids, meibomian gland dysfunction may not beobvious even when examined with the magnification of the slit-lampbiomicroscope, since there may not be external signs or the externalsigns may be so minimal that they are overlooked. The external signs ofmeibomian gland dysfunction without obvious lid inflammation may belimited to subtle alterations of the meibomian gland orifices,overgrowth of epithelium over the orifices, and pouting of the orificesof the glands with congealed material acting as obstructions. In severeinstances of meibomian gland dysfunction without obvious lidinflammation the changes may be obvious, including serrated or undulatedlid margins, orifice recession and more obvious overgrowth of epitheliumover the orifices, and pouting of the orifices.

Hormonal changes, which occur during menopause, and particularlychanging estrogen levels, can result in thickening of the oils secretedby the meibomian glands which results in obstructed meibomian glandsducts and orifices. Further, decreased estrogen levels may also enhanceconditions under which staphylococcal bacteria can proliferate. This cancause migration of the bacteria into the glands, thus resulting in adecreased secretion rate.

When the flow of secretions from the meibomian gland is restricted dueto the existence of an obstruction, cells on the eyelid margin have beenobserved to grow over the gland orifice thus further restricting sebumflow and exacerbating the dry eye condition. Additional factors whichmay cause or exacerbate meibomian gland dysfunction include, age,disorders of blinking, activities such as computer use which compromisenormal blinking, contact lens wear and hygiene, cosmetic use, or otherillness, particularly diabetes.

The state of an individual meibomian gland can vary from optimal, whereclear meibomian fluid is produced; to mild or moderate meibomian glanddysfunction where milky fluid or inspissated or creamy secretion isproduced; to total blockage where no secretion of any sort can beobtained (see Korb, et al., “Increase in Tear Film Lipid Layer ThicknessFollowing Treatment of Meibomian Gland Dysfunction”, Lacrimal Gland,tear Film, ad Dry Eye Syndromes, pp. 293-298, Edited by D. A. Sullivan,Plenum Press, New York (1994)). Significant chemical changes of themeibomian gland secretions occur with meibomian gland dysfunction andconsequently, the composition of the naturally occurring tear film isaltered, which in turn, contributes to ocular disease which is generallyknown as “dry eye”.

While the tear film operates as a singular entity and all of the layersthereof are important, the lipid layer, which is secreted from themeibomian glands, is of particular significance as it functions to slowthe evaporation of the underlying layers and to lubricate the eyelidduring blinking which prevents dry eye.

It is noted that partial obstruction in incipient stages may not lead todetectable dysfunction until obstruction crosses a threshold ofdetectable glandular efficacy—analogous to coronary occlusion fromincipient to infarction.

It is further noted that the term “dropout” is used to refer to absenceof one or more glands due to congenital, surgical or atrophic factors.Dropout is presently the word used to describe the partial or completeabsence of the meibomian gland(s).

To summarize, the meibomian glands of mammalian (e.g., human) eyelidssecrete oils that prevent evaporation of the tear film and providelubrication to the eye and eyelids. These glands can become blocked orplugged by various mechanisms leading to so-called “dry eye syndrome”.While not the only cause, meibomian gland dysfunction (MGD) is known tobe a major cause of dry eye syndrome. The disorder is characterized by ablockage of some sort within the meibomian glands or at their surfacepreventing normal lipid secretions from flowing from the meibomianglands to form the lipid layer of the tear film.

Such secretions serve to prevent evaporation of the tear film andlubricate the eye and eyelids, hence their absence can cause dry eyesyndrome. Obstructions or occlusions of the meibomian glands may bepresent over or at the orifice of the gland, in the main channel of thegland which may be narrowed or blocked, or possibly in other locationsincluding the passages from the acini to the main channel.

It has been theorized that the acini of the glands may have valves attheir junction with the main channel of the gland. The inventorstheorize that if these valves exist, they may also become obstructed insome instances leading to reduced or blocked flow from the acini. Theseobstructions or occlusions may have various compositions.

In response to the foregoing, various treatment modalities have beendeveloped in order to treat the dry eye condition, including drops whichare intended to replicate and replace the natural tear film,pharmaceuticals which are intended to stimulate the tear producingcells, and various heating devices which are designed to assist inunclogging the meibomian glands. Other techniques involve manualexpression of the glands.

Eye drops such as Refresh®, Soothe® and Systane® brand eye drops aredesigned to closely replicate the naturally occurring healthy tear film.However, their use and administration is merely a treatment of symptomsand not of the underlying cause. Further, the use of drops is generallyfor an indefinite length of time and consequently, extended use canbecome burdensome and costly.

Pharmaceutical modalities such as the use of tetracycline have also beensuggested to treat meibomian gland dysfunction and one such treatment isdisclosed in United States Patent Publication no. US2003/011426 titled“Method for Treating Meibomian Gland Disease”, U.S. Pat. No. 6,455,583titled “Method for Treating Meibomian Gland Disease” to Pflugfelder etal. and PCT Publication No. WO 99/58131 titled “Use of Tetracyclines forTreating Meibomian Gland Disease”. However, this treatment has notproven to be universally clinically effective, and it may be unnecessaryin cases where meibomian gland dysfunction is the result of obstructionof the gland without infection. The use of corticosteroids have alsobeen proposed to treat meibomian gland dysfunction as disclosed in U.S.Pat. No. 6,153,607 titled “Non-preserved Topical Corticosteroid forTreatment of Dry Eye, filamentary Keratitis, and Delayed Tear Clearance(or Turnover) to Pflugfelder et al. Again, this proposed treatmentappears to treat the symptom of dry eye, as opposed to treatment of theunderlying cause. Additionally, the use of topically applied androgensor androgen analogues have also been used to treat acute dry eye signsand symptoms in keratoconjuctivitis sicca as disclosed in U.S. Pat. No.5,958,912 and U.S. Pat. No. 6,107,289 both titled “Ocular Therapy inKeratoconjunctivitis Sicca Using Topically Applied Androgens or TGF-β”and both issued to Sullivan.

Most knowledgeable doctors agree that heat is beneficial in treatingMGD. Depending upon the nature of the obstruction, heat may bebeneficial in actually melting or loosening the obstructing material,permitting the gland to begin production and excretion of lipids andother fluids more freely.

One modality for the heat treatment of meibomian gland dysfunction isdisclosed in European Patent Application serial no. PCT/GB2003/004782titled “Eyelid Margin Wipes Comprising Chemical Means for TemperatureAdjustment”. As disclosed in this patent application, a wipe is providedwherein prior to use, a chemical agent is activated that will heat thewipe to about 32° C. to about 40° C. The hot wipe is then applied to thelids and manual expression can then be used to unclog the ducts. Thismethod is not without its drawbacks in that lid irritation can beexacerbated by non-specific heating.

Another method of heating the eyelids and meibomian glands uses nearinfrared (NIR) radiation. More specifically, two hard eye patches wereattached to an eye mask according to the pupillary distance of thesubject. The eye mask was held in place by an elastic headband. Eachpatch employed 19 light emitting diodes, emitting near infraredradiation from 850 nm to 1050 nm, with a peak at 940 nm. The deviceproduced 10 mW/cm² of energy operating on electrical power. Goto, E., etal., Treatment of Non-Inflamed Obstructive Meibomian Gland dysfunctionby an Infrared Warm Compression Device, British Journal of Opthalmology,Vol. 86 (2002), pp. 1403-1407. This device is designed as a non-contactinfrared heating mask using IR light emitting diodes. However, there aremany potential problems with use of an IR heating mechanism. Forexample, the IR Heat can penetrate beyond the eyelid into the corneawhich is undesirable, and could ultimately cause cataracts or otherdamage. Additionally, the IR mask heater places no pressure whatsoeveron the eyelid (despite the description as a compression device) which wehave determined is useful to expel the blockage. Moreover, testsconducted on a sample of this mask revealed that in spite of thepotential dangers, the mask produced very little actual heat. Andfurthermore, the device has no way of knowing how hot the tissue isgetting. The temperature of the tissue and that of the meibomian glandsbeing treated depends upon blood flow rate in the eyelid as well aseyelid thickness which are different from patient to patient.

United States Patent Publication US2004/0237969 titled “Therapeutic Eyeand Eye Lid Cover” comprises a pair of goggles that are adapted todeliver heated saturated air to the eyelids and particularly to themeibomian glands, again to heat the gland. Heat treatment of the eyes isalso discussed in the article titled “Tear Film Lipid Layer Thicknessand Ocular Comfort after Meibomian Therapy via Latent Heat with a NovelDevice in Normal Subjects by Mitra et al, published in Eye, (2004) atpages 1-4. The problems associated with this invention are similar tothose of the IR goggles in that no pressure or force is administered tothe glands during heating.

United States Patent Publication US2003/0233135 titled “Method andApparatus for Preventing and Treating Eyelid Problems” to Yee attemptsto clear the plugged meibomian glands by means of electrical stimulationof the muscle of Riolan which the invention presumed to aid in theexpression of the meibomian gland secretion.

SUMMARY OF CERTAIN EMBODIMENTS

In view of the above, a need for an imaging technique for imaging theeyelid, and particularly the meibomian glands of the eyelids is needed.It is therefore an object of embodiments consistent with the presentinvention to provide an imaging method and apparatus for illuminating orimaging mammalian eyelids including meibomian glands.

It is a further object of certain embodiments to provide images of themeibomian glands.

It is another object of certain embodiments to provide illuminating andimaging techniques that produce images that can be stored and laterretrieved or displayed.

It is still another object of embodiments consistent with the presentinvention to provide a method of illuminating or imaging meibomianglands that can be used to view or produce images that can be used tocompare before and after treatment of the meibomian glands to determinea degree of effectiveness of treatment.

These and other objects and advantages will become evident upon reviewof the embodiments disclosed. It is noted that not all embodimentsdisclosed, taught or claimed herein necessarily meet each one of theobjectives noted above, but that in no way should be construed to placethe embodiment within or outside of the bounds of the inventionspresented herein.

A method of near infrared (NIR) imaging of a meibomian gland consistentwith certain illustrative embodiments involves illuminating themeibomian glands with NIR radiation using an NIR light source; focusingan NIR camera on a region of an eyelid containing the meibomian gland;making a first NIR image of the meibomian gland; applying a pressuresuitable for simulating blinking pressure on the meibomian gland;optionally refocusing the NIR camera on the region of the eyelidcontaining the meibomian gland; and making a second NIR image of themeibomian gland while the pressure is being applied.

In certain embodiments, the NIR camera has an objective lensmagnification of between about 60× and 10× between about 650 and 900 nmwavelength. As an example the range of 16× to 25× is the most commonrange used with a slit lamp for imaging one or several glands. However,it would also be desirable to image the entire lid to see the generalcharacteristics of all of the meibomian glands. In certain embodiments,the imaging is carried out using NIR optical imaging approximately inthe 0.650 to 2.5 micron wavelength range. In certain embodiments, theimaging is carried out using trans-illumination photography. In certainembodiments, the trans-illumination is produced by oblique illuminationof the eyelid from an anterior surface thereof. In certain embodiments,the trans-illumination is produced by lighting the eyelid from aposterior surface thereof. In certain embodiments, thetrans-illumination is produced by use of a scleral lens serving as alight source from the posterior surface of the eyelid. In certainembodiments, the trans-illuminating is carried out using a lenspiececomprises an array of light emitting elements mounted to a substratesuitable for contact with eyeball. In certain embodiments, the NIRradiation includes radiation having wavelength that is either absorbedor transmitted preferentially through lipid rich material versus tissuesurrounding lipid rich tissue. In certain embodiments, at least one ofthe imaging and re-imaging is carried out while pressure is applied tothe eyelid that simulates an amount of pressure caused by blinking theeyelid.

In another illustrative embodiment, a method of imaging a mammalianmeibomian gland or other section of an eyelid involves shining a nearinfrared light on the eyelid in order to trans-illuminate at least aportion of the eyelid with NIR illumination; and from the outer surfaceof the eyelid, imaging the trans-illuminated portion of the eyelid usingNIR microscopic imaging.

In certain embodiments, the shining and capturing are repeated at anadjacent location of the outer surface of the eyelid and furthercomprising combining the images from the first and adjacent locations.In certain embodiments, the combining is selected from the groupconsisting of stitching, adding, and averaging the images from the firstand adjacent locations to produce a resultant image of a larger area ofthe eyelid. In certain embodiments, the NIR microscopy imaging iscarried out using a camera having an objective lens magnification ofbetween about 60× and 10× between about 650 and 900 nm wavelength. Incertain embodiments, the imaging is carried out using NIR opticalimaging in approximately the 0.650 to 2.5 micron wavelength. In certainembodiments, the trans-illumination is produced by lighting the eyelidfrom a posterior surface thereof. In certain embodiments, thetrans-illumination is produced by use of a scleral lens serving as alight source from the posterior surface of the eyelid. In certainembodiments, the trans-illumination is produced by use of a contactlenspiece comprising an array of light emitting elements mounted to asubstrate suitable for contact with eyeball. In certain embodiments, theNIR radiation includes radiation having wavelength that is eitherabsorbed or transmitted preferentially through lipid rich materialversus tissue surrounding lipid rich tissue.

In another illustrative embodiment, a method of imaging a mammalianpatient's meibomian gland or other section of an eyelid of an eyeinvolves placing a contact light source in contact with the eye; havingthe patient close the eye; illuminating the contact light source lightemitting from the light source through the eyelid from the posteriorsurface of the eyelid to trans-illuminate a portion of the eyelid; andfrom the outer surface of the eyelid, imaging the trans-illuminatedportion of the eyelid.

In certain embodiments, the process further involves repeating theillumination and capturing of an image at a second location on theeyelid, and processing the images to produce a single composite image.In certain embodiments, the contact light source produces NIR light andwherein imaging is carried out using a NIR camera having an objectivelens magnification of between about 60× and 10× between about 650 and900 nm wavelength. In certain embodiments, the imaging is carried outusing NIR optical imaging in approximately the 0.650 to 2.5 micronwavelength. In certain embodiments, the trans-illumination is producedby lighting the eyelid from a posterior surface thereof. In certainembodiments, the trans-illumination is produced by use of a scleral lensserving as a light source from the posterior surface of the eyelid. Incertain embodiments, the trans-illumination is produced by a contactlenspiece that comprises an array of light emitting elements mounted toa substrate suitable for contact with eyeball. In certain embodiments,the NIR radiation includes radiation having wavelength that is eitherabsorbed or transmitted preferentially through lipid rich materialversus tissue surrounding lipid rich tissue.

In another illustrative embodiment, an apparatus for imaging a portionof a mammalian eyelid has a light source suitable for directing nearinfrared light to a portion of the eyelid to illuminate a portion of theeyelid. A microscopic optical receiver suitable for receiving light fromthe eyelid and producing an output signal depicting an NIR image of theeyelid, the microscopic optical receiver receives light from the outersurface of the eyelid. An image processor receives the output signalthat captures an image from the light receiver.

In certain embodiments, the light source is arranged to provide obliqueillumination in order to trans-illuminate the portion of the eyelid. Incertain embodiments, the light source directs light to the portion ofthe outer surface of the eyelid via a first optical fiber. In certainembodiments, the optical receiver receives light from the outer surfaceof the eyelid via a second optical fiber. In certain embodiments, thetrans-illumination is produced by lighting the eyelid from a posteriorsurface thereof. In certain embodiments, the light source comprises ascleral lens serving as a light source from the posterior surface of theeyelid. In certain embodiments, the light source produces light havingwavelength that is either absorbed or transmitted preferentially throughlipid rich material versus tissue surrounding lipid rich tissue. Incertain embodiments, the light source comprises a lenspiece having anarray of light emitting elements mounted to a substrate suitable forcontact with eyeball. In certain embodiments, the light source directslight to the portion of the outer surface of the eyelid via a firstoptical fiber, and wherein the optical receiver receives light from theouter surface of the eyelid via a second optical fiber, and wherein thefirst and second optical fibers are positioned in a fixed geometricrelationship with one another.

In another illustrative embodiment, an apparatus for imaging a portionof a mammalian eyelid has an eye contact lenspiece configured to directthe light through an eyelid from posterior to anterior surface tothereby trans-illuminate the eyelid, when the light source illuminatesthe contact lens. An imaging device receives an image of the eyelid asit is trans-illuminated.

In certain embodiments, an image processor, receiving an output signalfrom the camera and processes the output signal to enhance the image. Incertain embodiments, the light source comprises an infrared light sourceand wherein the imaging device is compatible with infrared light. Incertain embodiments, the light source comprises a visible light sourceand wherein the imaging device is compatible with visible light. Incertain embodiments, the trans-illumination is produced by lighting theeyelid from a posterior surface thereof. In certain embodiments, thelight source comprises a scleral lens serving as a light source from theposterior surface of the eyelid. In certain embodiments, the lightsource produces light having wavelength that is either absorbed ortransmitted preferentially through lipid rich material versus tissuesurrounding lipid rich tissue. In certain embodiments, the light sourcecomprises a lenspiece having an array of light emitting elements mountedto a substrate suitable for contact with eyeball.

in another exemplary embodiment, an apparatus for imaging a portion of amammalian eyelid has a light source configured to direct near infraredlight through an eyelid to thereby trans-illuminate the eyelid. A NIRmicroscopic camera records an image of the eyelid as it istrans-illuminated. The light source is automatically positioned at aplurality of locations adjacent the eyelid and records a plurality ofimages at each of the plurality of locations using the camera. Aprocessor averages the plurality of images to produce a resultant image.

In certain embodiments, the NIR microscopic camera has an objective lensmagnification of between about 60× and 10× between about 650 and 900 nmwavelength. In certain embodiments, the imaging is carried out using NIRoptical imaging in approximately the 0.650 to 2.5 micron wavelength. Incertain embodiments, the trans-illumination is produced by lighting theeyelid from a posterior surface thereof. In certain embodiments, thelight source comprises a scleral lens serving as a light source from theposterior surface of the eyelid. In certain embodiments, the lightsource comprises a lenspiece having an array of light emitting elementsmounted to a substrate suitable for contact with eyeball. In certainembodiments, the light source produces light having wavelength that iseither absorbed or transmitted preferentially through lipid richmaterial versus tissue surrounding lipid rich tissue.

In another exemplary embodiment, an apparatus for facilitatingtrans-illumination of an eyelid covering an eye has an eye shield havingcurvature that is configured to approximately match a portion of acurvature of the external surface sclera of the eye, the eye shieldhaving an inner surface that contacts the eye and an outer surface. Theeye shield has properties that render the eye shield opaque to light ofa particular spectrum. An array of light sources is disposed on theouter surface to produce light in the particular spectrum in order totrans-illuminate the eyelid from a posterior side of the eyelid.

In certain embodiments, the array of light sources comprises an array oflight emitting diodes (LEDs). In certain embodiments, the LEDs comprisesurface mount LEDs. In certain embodiments, a flexible circuit board isaffixed to the outer surface and wherein the LEDs in the array of LEDsare attached to the flexible circuit board. In certain embodiments, anouter mold covers the array of LEDs in a manner that produces a smoothsurface. In certain embodiments, the flexible circuit board isreflective of light of the specified spectrum. In certain embodiments,an outer mold covers the array of light sources in a manner thatproduces a smooth surface. In certain embodiments, the outer mold haslight filtering or diffusing properties. In certain embodiments, theouter mold is transparent to the light of the particular spectrum. Incertain embodiments, an electrical connector provides electrical currentto the array of light sources. In certain embodiments, means areprovided for supplying electrical current to the array of light sources.In certain embodiments, the outer surface is reflective of light of thespecified spectrum.

In another exemplary embodiment, an apparatus for facilitatingtrans-illumination of an eyelid covering an eye has an eye shield havingcurvature that is configured to approximately match a portion of acurvature of the external surface sclera of the eye, the eye shieldhaving an inner surface that contacts the eye and an outer surface. Theeye shield has properties that render the eye shield opaque to light ofa particular spectrum. A flexible circuit board is affixed to the outersurface. An array of surface mount light emitting diodes is disposed onthe flexible circuit board to produce light in the particular spectrumin order to trans-illuminate the eyelid from a posterior side of theeyelid. An outer mold covers the array of LEDs in a manner that producesa smooth surface. Electrical current is supplied to the array of LEDs.

In certain embodiments, the flexible circuit board is reflective oflight of the specified spectrum. In certain embodiments, the outer moldhas light filtering or diffusing properties. In certain embodiments, theouter mold is transparent to the light of the particular spectrum. Incertain embodiments, the outer surface is reflective of light of thespecified spectrum.

In another exemplary embodiment, an apparatus for facilitatingtrans-illumination of an eyelid covering an eye has an elongated handlehaving an end. An eye shield is affixed to the end of the handle, theeye shield having opposing lighting and shielding surfaces. The eyeshield has properties that render the eye shield opaque to light of aparticular spectrum. An array of light sources is disposed on thelighting surface to produce light in the particular spectrum in order totrans-illuminate the eyelid from a posterior side of the eyelid when theeye shield is placed between the eyelid and the eye, and simultaneouslyshield the eye from direct light emanating from the light sources. Theeye shield and the array of light sources are flat enough to fit betweenthe eyelid and the eye.

In certain embodiments, the array of light sources comprises an array oflight emitting diodes. In certain embodiments, the LEDs comprise surfacemount LEDs. In certain embodiments, a flexible circuit board is affixedto the lighting surface and wherein the LEDs in the array of LEDs areattached to the flexible circuit board. In certain embodiments, an outermold covers the array of LEDs in a manner that produces a smoothsurface. In certain embodiments, the flexible circuit board isreflective of light of the specified spectrum. In certain embodiments,an outer mold covers the array of light sources in a manner thatproduces a smooth surface. In certain embodiments, the outer mold haslight filtering or diffusing properties. In certain embodiments, theouter mold is transparent to the light of the particular spectrum. Incertain embodiments, the handle includes a source of electrical currentthat supplies electrical current to the array of light sources. Incertain embodiments, electrical current is supplied to the array oflight sources.

The above overviews are intended to illustrate some of the manyexemplary embodiments which will be best understood in conjunction withthe detailed description to follow, and are not intended to limit thescope or meaning of the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Certain illustrative embodiments illustrating organization and method ofoperation, together with objects and advantages may be best understoodby reference detailed description that follows taken in conjunction withthe accompanying drawings in which:

FIG. 1 depicts upper and lower human eyelids showing the meibomianglands.

FIG. 2 is a cutaway view of an illustrative meibomian gland 20.

FIG. 3 is a cutaway view of meibomian gland 20 illustrating a pluggedorifice.

FIG. 4 is another cutaway view of meibomian gland 20 illustratingapproximate positioning of the eyelid and the eyeball.

FIG. 5 is another cutaway view of meibomian gland 20 having a bulgingplug in its orifice when pressure is applied that is imaged in a mannerconsistent with certain embodiments of the present invention.

FIG. 6 is a flow chart of an exemplary orifice surface imaging processconsistent with certain embodiments of the present invention.

FIG. 7 is a two dimensional depiction of an image of an eyelid havingplugged meibomian glands prior to application of a pressure suitable forcausing physical deformities at or about the orifice in a mannerconsistent with certain embodiments of the present invention.

FIG. 8 is a two dimensional depiction of an image of an eyelid withplugged meibomian glands with a pressure applied to cause physicaldeformities at or about the orifice in a manner consistent with certainembodiments of the present invention.

FIG. 9 is a two dimensional depiction of an image of the eyelid of FIG.8 after treatment to unplug the meibomian glands with pressure againapplied to cause any remaining orifice obstructions to become observablein a manner consistent with certain embodiments of the presentinvention.

FIG. 10 is an example of a visualization system consistent with certainembodiments of the present invention.

FIG. 11 is an example of a method consistent with certain embodiments ofthe present invention.

FIG. 12 is an example of a diagnosis tree consistent with certainembodiments of the present invention.

FIG. 13 is a perspective view of a first embodiment of the meibomiangland evaluation tool according to the present invention.

FIG. 14 is a broken away side view of an embodiment of the meibomiangland evaluation tool according to the present invention.

FIG. 15 is a perspective view of another embodiment of the meibomiangland evaluation tool according to the present invention.

FIG. 16 is a broken away side view of an embodiment of the meibomiangland evaluation tool according to the present invention.

FIG. 17 is another view of an embodiment of the meibomian glandevaluation tool according to the present invention.

FIG. 18 is a cutaway side view of an embodiment of the meibomian glandevaluation tool according to the present invention.

FIG. 19 is an exploded view of an embodiment of the meibomian glandevaluation tool consistent with embodiments of the present invention.

FIG. 20 is a broken away side view of another embodiment of themeibomian gland evaluation tool according to the present invention.

FIG. 21 is a broken away side view of another embodiment of themeibomian gland evaluation tool according to the present invention.

FIG. 22 illustrates an exemplary optical Infrared imaging system forimaging meibomian glands in a manner consistent with certain embodimentsof the present invention.

FIG. 23 is an example representation of an IR image of an occludedmeibomian gland consistent with certain embodiments of the presentinvention.

FIG. 24 is a flow chart depicting an exemplary method of use for the IRvisualization techniques consistent with embodiments of the presentinvention, but with simple modification is applicable to any of thetechniques described herein.

FIG. 25 is an illustration of an exemplary system for obliqueillumination for trans-illumination imaging of an eyelid in a mannerconsistent with certain embodiments of the present invention.

FIG. 26 depicts an exemplary hand-held instrument for manual imaging ofa portion of the eyelid using oblique illumination consistent withcertain embodiments of the present invention.

FIG. 27 is an illustration of a trans-illumination system consistentwith certain embodiments of the present invention.

FIG. 28 is an illustration of an exemplary rear trans-illuminationsystem consistent with certain embodiments of the present invention.

FIG. 29 depicts another exemplary trans-illumination techniqueconsistent with certain embodiments of the present invention.

FIG. 30 is a circuit diagram for a trans-illumination apparatusconsistent with certain embodiments of the present invention.

FIG. 31 is a flow chart depicting an illumination or heating processhaving the burning of a fusible link at the end of the cycle in a mannerconsistent with certain embodiments of the present invention.

FIG. 32 illustrates a light array assembly consistent with certainembodiments of the present invention.

FIG. 33 illustrates a flex circuit used in an embodiment of the lightarray assembly consistent with certain embodiments of the presentinvention.

FIG. 34 is a cross-sectional view showing assembly of the flex circuiton the lenspiece and connector in a manner consistent with certainembodiments of the present invention.

FIG. 35 is an illustration of another embodiment of an eyepiece andlight array assembly consistent with the present invention.

FIG. 36 illustrates a combined light array assembly eyepiece with amechanism for producing pressure on the eyelid using a bladder in amanner consistent with certain embodiments of the present invention.

FIG. 37 depicts a hand held trans-illumination device consistent withcertain embodiments of the present invention.

FIG. 38 is a flow chart depicting a method of use for the visualizationtechniques consistent with embodiments of the present invention.

DETAILED DESCRIPTION

While this invention is susceptible of embodiment in many differentforms, there is shown in the drawings and will herein be described indetail specific embodiments, with the understanding that the presentdisclosure of such embodiments is to be considered as an example of theprinciples and not intended to limit the invention to the specificembodiments shown and described. In the description below, likereference numerals are used to describe the same, similar orcorresponding parts in the several views of the drawings.

The terms “a” or “an”, as used herein, are defined as one or more thanone. The term “plurality”, as used herein, is defined as two or morethan two. The term “another”, as used herein, is defined as at least asecond or more. The terms “including” and/or “having”, as used herein,are defined as comprising (i.e., open language). The term “coupled”, asused herein, is defined as connected, although not necessarily directly,and not necessarily mechanically. The term “program” or “computerprogram” or similar terms, as used herein, is defined as a sequence ofinstructions designed for execution on a computer system. A “program”,or “computer program”, may include a subroutine, a function, aprocedure, an object method, an object implementation, in an executableapplication, an applet, a servlet, a source code, an object code, ashared library/dynamic load library and/or other sequence ofinstructions designed for execution on a computer system, and may bestored in a form of software or firmware.

Reference throughout this document to “one embodiment”, “certainembodiments”, “an embodiment” or similar terms means that a particularfeature, structure, or characteristic described in connection with theembodiment is included in at least one embodiment of the presentinvention. Thus, the appearances of such phrases or in various placesthroughout this specification are not necessarily all referring to thesame embodiment. Furthermore, the particular features, structures, orcharacteristics may be combined in any suitable manner in one or moreembodiments without limitation.

The term “or” as used herein is to be interpreted as an inclusive ormeaning any one or any combination. Therefore, “A, B or C” means “any ofthe following: A; B; C; A and B; A and C; B and C; A, B and C”. Anexception to this definition will occur only when a combination ofelements, functions, steps or acts are in some way inherently mutuallyexclusive.

As noted above, dry eye states have many etiologies. A common cause ofcommon dry eye states is the condition known as “meibomian glanddysfunction”, a disorder where the glands are obstructed or occluded. Asemployed herein the terms “occluded” and “obstruction” as they relate tomeibomian gland dysfunction are defined as partially or completelyblocked or plugged meibomian glands having a solid, semi-solid orthickened congealed secretion and/or plug of any composition, leading toa compromise, or more specifically, a decrease or cessation ofsecretion. Also with a reduced or limited secretion the meibomian glandmay be compromised by the occluded or obstructive condition as evidencedby a yellowish color indicating a possible infective state, or may beotherwise compromised so that the resulting protective lipid film of thetear film layer is not adequate.

Imaging of the meibomian glands of the human eyelid as well as imagingwhile simultaneously applying pressure to mimic the normal expression ofsecretion from the meibomian glands by blinking enables study of thedynamic function of the meibomian glands and resulting pathology. Theimaging of the meibomian glands while simultaneously applying pressurepermits the viewing of the anatomical features of the gland with andwithout pressure and the observation of the effects of the pressure onthe movement of the secretory material within and out of the gland. Thelatter observations permit the diagnosis of gland dysfunction andobstruction and the specific diagnosis of the site of the pathologywithin the gland or over the gland orifice.

As noted earlier, each meibomian gland has a straight long central ductlined with four epithelial layers on the inner surface of the duct.Along the length of the central duct there are multiple lateralout-pouching structures, termed acini where the secretion of the glandis manufactured. The inner lining of each acinus differs from the maincentral duct in that these specialized cells manufacture the secretionsof the meibomian gland. The secretions flow from each acinus to theduct. While currently it has not been established with certainty, thereappears to be a valve system between each acinus and the central duct toretain the secretion until it is required, at which time it isdischarged in to the central duct. The meibomian secretion is thenstored in the central duct and is released through an orifice of eachgland onto the surface of the eyelid at the eyelid margin. The centralduct leading to the orifice is on the order of 100 microns or less indiameter. Blinking and the squeezing action of the muscle of Riolansurrounding the meibomian glands are currently believed to be theprimary mechanism to open the orifice for the release of secretion fromthe meibomian gland.

There is currently no truly acceptable method of imaging the meibomiangland and related structures or other abnormalities of the eyelid inorder to evaluate the function of the glands. Moreover, there iscurrently no truly acceptable mechanism to evaluate the dynamic functionand resulting pathology of the meibomian gland.

In order to better understand the dynamic function and resultingpathology of the meibomian glands, certain embodiments consistent withthe present invention utilize the application of varying levels ofpressure to the glands in order to observe the gland when a pressurecomparable to that exerted by the blink is applied over the meibomianglands. The pressures of the lids during normal blinking areminimal—perhaps on the order of only several grams per square mm ofpressure. Many individuals with dry eye conditions practice forcedblinking where the lids are squeezed together tightly with maximumpressure as an aid in expression of the meibomian secretion which arenot adequately expressed with normal blinking due to partial meibomiangland obstruction. It should also be noted that there may be a widevariance in the efficacy of the approximately 50 meibomian glands ofboth eyelids, where some glands will be totally obstructed, somepartially obstructed with minimal secretion, and some with varyingdegrees of normal secretion.

The application of a pressure of varying degrees to the external surfaceof the eyelids while simultaneously imaging the meibomian glands allowsthe visualization of the dynamic status of the gland relative to thefollowing:

Whether the secretory material with the application of a pressure to theexternal lid flows from the acini to the central duct or the secretorymaterial is trapped and stagnated within the acini. One cause for thisis an obstruction in valves that may be present in the acini at theirjunction to the central duct.—According to literature Mansour (1988)along with Virchow (1910) and Dryja (1986) published on valves in theMeibomian gland. Mansour described the valves and postulated that if thevalves malfunctioned, chalazia might occur. (Mansour A M (1988).Meibomian Gland Secretion. Orbit—An International Journal On OrbitalDisorders And Facial Reconstructive Surgery 7 (3): 201-209.)

Chalazion is usually thought of a swelling, engorgement or increase insize of a meibomian gland and pertinent descriptions and definitionsfollow: Patients will generally present with one or many focal, hard,painless nodules in the upper or lower eyelid. They may report someenlargement over time, and there may be a history of a painful lidinfection prior to the chalazion development, but this isn't always thecase. A chalazion is a non-infectious, granulomatous inflammation of themeibomian glands. The nodule itself consists of many types ofsteroid-responsive immune cells, including connective tissue macrophagesknown as histiocytes, multinucleate giant cells, plasma cells,polymorphonuclear leukocytes and eosinophils. A chalazion may be aresidual aggregation of inflammatory cells following an eyelid infectionsuch as hordeola and preseptal cellulitis, or may develop from theretention of meibomian gland secretions.

Heretofore, this observation and diagnosis has never been reported. Itmay also be possible to observe the anatomical features which regulateflow from the acini into the central duct and their actions observedunder application of varying pressures leading to a diagnosis that willfacilitate treatment methods.

The central duct should be open without obstruction or adhesions andcontain the liquid contents of the secretions from the acini. Imagingand observation will identity the nature and the location of anyobstruction or adhesion. The diagnosis of the status of the central ducthas never been reported (other than with biopsy specimens). Imaging ofthe central duct will facilitate development and utilization oftreatment methods.

The central duct should discharge the secretory contents through theorifice onto the lid margin and to the tear film with the application ofa pressure to the external lid mimicking the pressures of a blink. Thedischarge occurs through the orifices of the meibomian glands, which aresituated in the lid margin and are closed unless a pressure is appliedeither through blinking or by manual means. Imaging of the glandsimultaneously with the application of pressure will reveal the flowcharacteristics within the gland and the nature of the flow through thecentral duct and the terminal duct ending at the orifice.

If the application of a pressure to the external lid does not result inthe expression of secretion from the gland, appropriate imaging willreveal whether the application of the pressure results in a pouting,bulging or a change in shape of the orifice. When the secretory materialis compressed into the orifice, if there is overgrowth of tissue overthe gland orifice, there will be pouting or other physical deformationof the contents at the end of the orifice, the pouting resulting fromthe overgrowth of epithelium over the gland which will extend with thepressure from the compression of the contents. This indicates that theprimary obstructive process is not primarily within the duct, but is theresult of obstruction of the duct by the overgrowth of epithelium of thelid margin over the duct. Secondary obstruction within the duct willthen occur, since the secretions are unable to be discharged due to theobstruction over the orifice on the lid margin. Specific treatment torelieve the overgrowth is therefore indicated. If on the other handthere is no pouting of the gland or other physical deformation at theorifice surface, the obstruction would more likely be internal, and thelocation of such obstruction would advantageously be shown by certain ofthe imaging techniques consistent with certain embodiments of thepresent invention (or could at least be deduced by a lack of observablepouting or other deformities of the orifice). Treatment could thentherefore be directed to the internal cause.

Application of pressure also may result in secretion of materials whosecolor, consistency and other characteristics can facilitate diagnosis.

Meibomitis, an inflammation of the meibomian glands leading to theirdysfunction, is usually accompanied by blepharitis (inflammation of thelids). Meibomian gland dysfunction may accompany meibomitis, ormeibomian gland dysfunction may be present without obvious lidinflammation. Meibomian gland dysfunction is frequently the result ofkeratotic obstructions which partially or completely block the meibomiangland orifices and/or the central duct (canal) of the gland andcompromise the secretory functions of the individual meibomian glands.More particularly, these keratotic obstructions can comprise combinationof bacteria, sebaceous ground substance, dead, and/or desquamatedepithelial cells. While meibomitis is obvious by inspection of theexternal lids, meibomian gland dysfunction may not be obvious even whenexamined with the magnification of the slit-lamp biomicroscope, sincethere may not be external signs or the external signs may be so minimalthat they are overlooked. The external signs of meibomian glanddysfunction may be limited to subtle alterations of the meibomian glandorifices, overgrowth of epithelium over the orifices, and pouting of theorifices of the glands with congealed material acting as obstructions,for example.

In view of the difficulty of diagnosis of the function of the meibomianglands by the usual slit-lamp visual inspection utilizing magnification,and the lack of existing criteria for evaluation of the degree ofdysfunction of the meibomian glands, the inventors have determined thatthere is a need for imaging techniques that can be employed in thediagnostic processes. While imaging of various portions of the humananatomy have been studied and developed extensively, techniques forsuitable imaging the meibomian glands of a living subject, other thanthe slit-lamp magnified visual examination, are non-existent.Illuminating and imaging of the meibomian glands present unusual andspecific problems.

Several different mechanisms can be provided for imaging the eyelid toprovide imaging to assist in diagnostic as well as pre and posttreatment evaluation of the proper function of the meibomian glands ofthe eyelid. While the human eye is of greatest interest, the techniquesdescribed herein may also be applied to other mammalian eyelids as wellas other similar glands, with human eyes being referenced by way ofexample herein.

The typical human eyelid is less than 5 mm in thickness, and is mostoften less than about 4 mm in thickness. An eyelid that is 5 mm or morein thickness constitutes a quite thick eyelid for a human subject. Theupper eyelid contains approximately 25-30 meibomian glands while thelower eyelid contains approximately 20-25 meibomian glands. In mostinstances, the meibomian glands are situated within the eyelidapproximately ⅔ of the way from the front to the rear of the eyelid. Thecentral tube of a small sample of glands that have been measured areroughly 100 microns in diameter (with a great deal of variationanticipated since only a limited number of glands have actually beenmeasured at this writing). Also to identify a full or partial meibomiangland obstruction, either fully or partially, the imaging shouldpreferably have a resolution down to approximately 1 to 10 microns with1 to 5 being desired. This presents a rather unusual imaging problem inthat the gland is quite small, is situated on a curved surface, islocated at a very sensitive part of the body and requires rather highresolution imaging to actually observe. Hence, one or more techniquesthat can be used with relative comfort to the patient and which resultin resolution that is high enough to be of value to the clinician areneeded. Imaging these glands is further complicated by the relativelysmall size of the glands and lack of clear reference points to identifyone particular gland and distinguish it from other glands. Currently, nonumbering or other identification system to isolate a single glandexists, partially due to the variation in number of such glands, anddifficulty in establishing standards in the absence of satisfactoryimaging.

As noted, these glands can become obstructed or clogged to producevarying degrees of “dry eye syndrome”. Normally, the meibomian glandsproduce clear oil which, together with tears, serves to keep the eyelubricated and cleansed. However, meibomian glands can become cloggedfor a variety of reasons (many even potentially unknown). In suchcircumstances, the secretion of natural oils is inhibited or stoppedaltogether. The obstructive materials or plugs that occlude the glandswhen examined after their expression from the gland take on variousphysical appearances including, but not limited to, clear gel, apetroleum jelly like appearance, milky colored or hard white wire-likeappearance. Also the physical appearance is dependent upon temperatureand can be oil; inspissated jelly like; globular or bead like;filamentary from thin wire like to thicker filaments resembling toothpaste expressed from the tube. The color can be clear, tinged off whitevarying to yellow indicating infection and pus. Each such obstruction,whether total or partial, reduces the amount of oil available tolubricate the eye, leading to increased evaporation of the tear film,and inflammation and/or discomfort and dry eye states when the number ofcompromised meibomian glands fails to provide an adequate lipid layer tomaintain the tear film.

In most instances the lower eyelids are of most interest since theyappear to generally be a primary source of secretion of the naturaloils, and are most frequently the culprit when a patient presents withdry eye syndrome related to occluded meibomian glands. The upper eyelidstend to be less problematic—perhaps due to their movement duringblinking or gravity assisting in the flow of lipids therefrom.

Current diagnosis techniques are limited to microscopic visualinspection of the top of the glands at the lid margin, ortrans-illumination by inverting the eyelid and viewing the eyelid fromthe inner surface (which has been inverted for viewing—which presentsdifficulty for the physician in manipulation of the eyelid and patientdiscomfort). There is no known technique that can provide imaging thatcan provide before and after images in order to assess the success ofany given treatment. The lack of a consistent diagnosis tool to obtainbefore and after comparison images of the operation of the glands andtreatment success further leads to problems in insurance reimbursementfor the physician.

Several variations of visualization of the meibomian glands arepresented herein. It will be understood that many variations of theembodiments taught will be evident to those skilled in the art uponconsideration of the present teachings. Each of the technologiesdescribed herein can be implemented using either stationary apparatusinto which the patient places his or her eye during imaging (e.g., withstabilization of the patient's head by chin and forehead rests), andhandheld apparatus which is placed in appropriate proximity to theeyelid by the physician or technician during testing.

Referring now to FIG. 1, the location of the meibomian glands 20 areshown on the upper and lower eyelids 22 and 24 respectively. As brieflystated herein above, the upper lid contains about 25 meibomian glandsand the lower lid contains about 20 meibomian glands, with significantvariation. As shown in cross-sectional view of one gland 20 in FIG. 2,each gland includes a central duct or channel 28 into which thesecretion flows from acini 29 and an orifice 30 which opens on to theeyelid margin and through which the secretion flows in order to be addedto the tear film upon blinking. It will be seen that the glands are ofdifferent size, depending upon the location in the eyelid and that theorifice 30 is narrower than the central duct 28.

Obstruction composition will vary with the etiology which produced it.However, the obstruction will, in most cases observed to the present, bea combination of, dead cells, bacteria, desquamated cells, desquamatedcells aggregating in keratotic clusters, milky fluid, inspissated orcreamy secretions, or any combination of the foregoing in solid,semi-solid and thickened forms. Referring to FIG. 3, a simplified viewof exemplary obstructions to gland 20 is depicted. In this example,which is by no means necessarily representative of all meibomian glandobstructions, as explained above, a solid or semi-solid or thickenedplug 34 is depicted which is fully occluding the orifice 30 of gland 20.Another obstruction 36 is shown at a junction from one of the acini withthe central duct. As previously noted, this may be the site of a valvein the gland structure, but embodiments consistent with the presentinvention should not be limited by theories of the actual meibomiangland structure.

Surface Imaging

One mechanism for providing imaging of meibomian glands for bothdiagnosis and post treatment evaluation is depicted in FIGS. 4-9. FIG. 4depicts a cutaway view of meibomian gland 20 illustrating approximatepositioning of the lower eyelid 24 and the eyeball 42. Details such asthe eyelashes have been omitted for illustrative clarity. In someinstances, microscopic observation can detect the presence of a plug 34in meibomian gland 20, or adjacent meibomian glands. However, in manyinstances, simple visual observation is inadequate to clearly documentand specifically identify the location or locations of an occludedmeibomian gland 20, particularly depending upon the nature of the plug34. It is also noted that magnification levels of 25× to 50× at leastare advantageous in observation of the orifice at the surface of ameibomian gland. However, such high magnification is difficult to usedue to the great exaggeration of even very small movements of thepatient.

However, plugged glands such as gland 20 can be more readily identifiedusing the technique illustrated in FIG. 5, which depicts another cutawayview of meibomian gland 20 having a bulging plug 34 or puckering orother physical deformation at the orifice 30 in its orifice that isimaged in a manner consistent with certain embodiments of the presentinvention. In this embodiment, a tool 46 (which may simply be a finger,but is preferably a calibrated instrument as will be described later) ispressed against lower eyelid 24 in a controlled manner, while the uppereyelid is held open, with the pressure illustrated by arrow 50. Thispressure compresses the eyelid from the anterior surface, and thus themeibomian gland 20 so that fluid present inside the gland 20, exertsupward pressure on the plug 34 to produce a bulge, pucker or otherphysical deformation at the surface of the eyelid at or about thelocation of the orifice as illustrated. This technique provides thephysician with an indication of the actual functioning of the glands.

Images can be made using a camera 54 with suitable magnification(depicted as 58), e.g., attached to an ophthalmologic microscope ormacro focus lens of suitable focal length, lighting and magnification toimage a desired region of the eyelid and freeze or minimize the effectsof patient movement. Flash photography or high light—high shutter speedphotography can be used to freeze motion if needed. In otherembodiments, pressure can be exerted from either or both the anteriorand posterior surfaces of the eyelid to thereby squeeze the meibomianglands. The application of pressure on the eyelid and imaging of thesecretion is also useful in diagnosis. Depending on the color,consistency and presence of the secretion one can categorize the amountof meibomian gland dysfunction (MGD). The state of an individualmeibomian gland can vary from optimal, where clear meibomian fluid isproduced; to mild or moderate meibomian gland dysfunction where milkyfluid or inspissated or creamy secretion is produced; to total blockagewhere no secretion of any sort can be obtained. As noted above,obstruction composition will vary with the etiology which produced it.However, the obstruction will, in most cases observed to the present, bea combination of, dead cells, bacteria, desquamated cells, desquamatedcells aggregating in keratotic clusters, milky fluid, inspissated orcreamy secretions, or any combination of the foregoing in solid,semi-solid and thickened forms.

A similar procedure can be carried out for imaging the upper eyelid,however it is believed at present that approximately 70% of dry eyeproblems are associated with meibomian gland dysfunction with the lowereyelid. Accordingly, diagnosis and treatment of the lower eyelid may beof most significance in many cases. However, this is not intended topreclude imaging of the upper or both eyelids.

FIG. 6 is a flow chart of an exemplary orifice surface imaging process68 consistent with certain embodiments of the present invention startingat 72. Many variations of this process are possible depending upon whatimages are desired for a particular purpose. At 74, camera 54 is focusedon the eyelid surface carrying the meibomian glands (in this example,the upper surface of the lower eyelid 24 at an angle suitable to produceperspective of the raised bulge or pucker or other physical deformation34 at the surface). If desired, at 78 an image can be generated at thisstage to document the normal state of the glands. Certain of the glandsmay appear clearly occluded in this image, but the image may not revealall occlusions (e.g., 36).

FIG. 7 is a two dimensional depiction of an image of the eyelid havingplugged meibomian glands at this stage of the process and prior toapplication of a pressure suitable for causing the plugs of themeibomian glands to bulge or the orifice to pucker or produce otherobservable physical changes in a manner consistent with certainembodiments of the present invention. For ease of illustration, theimage is depicted as being taken from approximately normal to the outersurface of the eyelid, rather than at an angle showing perspective ofthe surface containing the orifice. Any variety of angles can be usedfor the images depending upon the patient, diagnostician preferences,etc. This image, if desired and taken, can be used for reference and fordetection of obvious occlusions which show up as visible bulges orpuckers representing a plug which may produce a recognizable pattern andcolorations for comparison when a post treatment image is taken. Thisimage can also be compared with the image of FIG. 8 as will be describedlater, to determine the presence of occlusions that would not be visiblewithout application of pressure to create bulges or puckers 84 (ananalogous physical deformation at the surface wherein the tissuesurrounding a plugged orifice bulges around the plug to create a“pucker” effect) as illustrated.

Referring back to FIG. 6, at 86, a controlled pressure is applied tocause bulging or puckering or other physical deformation of occludedmeibomian gland orifices. This pressure can be applied in a number ofways as will be described later, but are generally in the range ofpressures that would simulate or mimic a patient blinking his eyes. Oncethe bulges or other physical deformations are apparent, at 90 they maybe imaged using camera 54 to produce, for example, an image as depictedin FIG. 8 which shows a two dimensional depiction of an image of aneyelid with plugged meibomian glands with a pressure applied to causethe plug 34 to bulge or pucker to produce the physical deformationsillustrated as 84 in FIG. 8 in a manner consistent with certainembodiments of the present invention. The images of FIGS. 7-8 can beused to gauge the degree, location and number of observabledysfunctional meibomian glands and to create a record thereof. Analogousrecords are often necessary to assure insurance reimbursement and toestablish nature and degree of occlusion of the meibomian glands fordiagnostic purposes.

Referring back to FIG. 6, a treatment can be conducted, as at 94, thesuccess of the treatment can also be gauged using post treatmentimaging. Thus, at 98, the camera can be refocused on the same eyelid andthe controlled pressure again applied at 102 to induce bulging orpuckering or other surface deformations at the orifice of occludedmeibomian glands. A post treatment image can then be made at 106 withthis exemplary process ending at 110.

FIG. 9 is a two dimensional depiction of an image of the eyelid of FIG.8 after treatment to unplug the meibomian glands with pressure againapplied as in 102 to cause any remaining obstructions to cause bulges orpuckers 84 (two depicted) in a manner consistent with certainembodiments of the present invention.

While the above description may be construed to imply the use of stillimages, moving images can also be utilized, for example, to produce apan across the eyelid at a microscopic level to image the entire eyelid.Alternatively, a suitably wide angle image with high enough visualresolution can be captured to provide ease of reference for relocationof clogged glands. The diagnostician may also apply markings to theeyelids to serve as reference points in the images to more readilyidentify a particular gland. It is additionally noted that the surfaceimage may be acquired using a light source to illuminate the eyelid in anumber of ways as will be described later. Such light source may be fullspectrum visible light, near infrared (NIR) or other suitable spectrumor combination of spectra. In one embodiment, the light spectrum can bechosen for minimum attenuation of light when passed through human tissuesuch as the eyelid.

In order to assure clarity of the microscopic images, the image shouldpreferably be produced under circumstances wherein the object beingimaged is as stable as possible with exposure times being minimized. Inthis case, the head can be stabilized in a conventional manner usingconventional ophthalmologic chin and forehead braces as are used inconventional ophthalmologic exams, with the examination braces fittedwith suitable visual light photography instruments as described herein.

FIG. 10 depicts a more detailed setup for visible light imagingaccording to certain embodiments in which camera 54 is used, throughsuitable magnification represented by 58, to capture an image of theeyelid (e.g., lower eyelid 24) and associated meibomian gland 20. Imagesfrom camera 54 may be rendered using either conventional photographicprocesses or can be directed to an image processing computer 208 thatcan then process and possibly enhance the image, for example by shiftingof brightness, color, gamma function, sharpness or contrast or by use oftomography. The image can then be displayed on a display monitor 212,and/or stored on disk or other storage 210, or printed on a photographicquality printer 216 or any or all of the above. In addition to stillimages, moving images can similarly be captured in this manner toproduce, for example, a pan across the eyelid in which individual framescan be captured and printed if desired. Due to the high magnification, astep and repeat process that captures a portion of the eyelid and thensteps across can be used, with focusing being carried out as the camerais swept about an arc to remain normal to a selected profile of surfacebeing imaged.

In certain embodiments, as further depicted in FIG. 10, a camera 54 andpossibly light source(s) (not shown) can be moved across the eyelid inan organized manner (i.e., in a suitable arc) using an X-Y or X-Y-Zcontroller 220 and a suitable servo motor arrangement 222 under controlof a programmed processor such as computer 208 in order to scan theentire eyelid. Scanning the eyelid can thus be accomplished manually orby use of an X-Y-Z control system. Similarly, the application ofpressure to the eyelid can be effected either manually, with manualcontrol determining when to create the image, or by coordinated actionof a pressure applying probe also operating under control of thecomputer 208 via servo control. In other embodiments, a single probedevice can apply pressure to the entire eyelid as the camera 54 ismanipulated manually or by step and repeat actions under control of thecomputer 208 in conjunction with controller 220 and servos 222. Manyvariations are possible without departing from embodiments consistentwith the present invention.

In order to provide references for identification of the meibomianglands, a reference scale or markings can be imaged along with thesurface in order to be able to later identify the location of particularglands.

FIG. 11 depicts an exemplary process 230 for imaging the meibomianglands in a manner consistent with certain embodiments of the presentinvention starting at 234 after which the camera 200 is focused on thesurface of the eyelid. One or more images are then created at 242 tocreate a pre-treatment reference image. This image may be processed asdescribed above, either by fully automated means or with the assistanceof manual intervention to highlight significant attributes by colormodification or enhancement by computer processing. The glands may thenbe treated using any suitable treatment mechanism at 246. Theeffectiveness of the treatment can then be evaluated by imaging theeyelid in the same manner as previously by refocusing the camera on theeyelid at 250 and re-imaging the eyelid and enhancing as needed at 254.The process ends at 260. A similar process can be used with any of theimaging techniques discussed herein.

Diagnosis of the condition can be made with a reasonable degree ofaccuracy using the present methods in conjunction with a decision systemsuch as the flow chart depiction of a decision tree 262 of FIG. 12starting at 264. At 266 where the physician or technician appliespressure to the eyelid adequate to mimic the pressure applied when aperson blinks. At 268, each meibomian gland is observed at the surfaceas the pressure is applied for results at 270. Any of several resultscan be observed as follows. No output from the individual MG at 272, nooutput from the individual MG accompanied by pouting or other physicaldeformation at the orifice when pressure is applied at 274, secretionoutput from the MG—but the secretion is not clear fluid at 276, or clearfluid output is secreted by the MG at 278.

When there is no output from the individual MG at 272, it can betentatively concluded that the individual MG is likely obstructed at280. When there is pouting or other physical deformity at the orifice,it can be concluded that the MG is likely obstructed and it is furtherlikely that the obstruction is at or near the orifice at 282. If theindividual MG secretes output, but it is not a clear fluid, at 276, itcan be concluded at 284 that the individual MG is likely compromised(e.g., by obstruction, inflammation, infection, etc.). When clear fluidis output from the MG at 278, the individual MG is likely to befunctioning normally or nearly normally at 286.

Since this assessment is made on a gland by gland basis, it is difficultfor a doctor or technician to make the assessment while continuallymoving and refocusing his microscope, and moving the probe used tosimulate the blinking pressure. Also, since the probe may repeatedlystimulate secretion from adjacent glands, it is possible to reduce ordeplete the available fluids from one or more glands, skewing the testresults. Hence, it is advantageous for the surface to be imaged duringthis process so that the assessment can be made on multiple glands witha single application of pressure and so that a reliable accounting forall or most glands can be made. This is extremely difficult to effectaccurately without imaging of the surface.

Once all of the glands have been imaged and the results evaluated foreach gland, an overall assessment can be made at 288. If almost all orall glands are obstructed at 288, it is likely that the patient hassevere MGD at 290. If a moderate number of the glands are obstructed at288, the likelihood is that the patient has moderate MGD at 292. If noneof the glands are obstructed or only a few are obstructed, the patientlikely has normal meibomian gland function at 294. The greater thenumber of obstructed or compromised meibomian glands, the more severethe MGD. It is difficult or impossible to provide an accurate absolutenumber of normally functioning glands that constitute normal MGfunction, since the number of glands per patient varies, as does theglandular output. Thus, some level of experience and judgment should befactored into the ultimate diagnosis. However, if all, or the greatmajority yield clear oil, there is probably no MGD.

At 296, other factors should be taken into consideration in making afinal determination as to the presence of MGD and its severity at 298.For example, it is possible for a gland to be normal, but all of thesecretion has been previously secreted during the day. In this case, theevaluation might not show any secretion upon the application of thepressure, but the gland would still be normal if it were evaluated earlyin the day before all of the secretion had been used. This may happenwith a few or with all of the glands at any given time. The later in theday or evening the greater the probability of this phenomenon, since thegland is believed to refill during sleep when there is no blinking andno normal secretion from the gland during sleep. Other factors that maybe considered are the age of the patient, observable inflammation ofgrowth over the orifice, history, hormonal conditions, etc.

Referring now to FIGS. 13 and 14 in which a first embodiment of a devicefor simulating blinking pressure on the eyelid is shown, the meibomiangland evaluation apparatus generally indicated at 300 comprises anelongate shaft or handle 305 having a bore 310 there through. Located atone end of handle 305 is an annulus 312 the purpose of which will becomeevident as the description proceeds. One end of handle 305 mounts a cap315 having a bore there through 317 and the opposite end of handle 305mounts a second end cap 320. The caps may be threaded, press fitted orotherwise connected, depending upon the particular fabrication techniqueand materials employed. For purposes of illustration only, cap 315 ispress fitted and cap 320 is threaded.

A probe tip 400 is mounted on shaft 325 for longitudinal movementrelative to the handle 305 such that when the probe tip 400 is placedagainst the eyelid and compressive force is applied, movement of thehandle 305 a preselected distance replicates the approximate forcerequired for natural expression of secretion from the meibomian gland.Testing has determined that this force is approximately 15 grams per 30mm² however; depending upon the age, gender, race or other factors, thisforce may vary somewhat and be between approximately 10 grams per 30 mm²and 20 grams per 30 mm². Probe tip 400 is detachably connected to oneend of a shaft 325 which is operatively associated with handle 305.Probe tip 400 is fabricated from a soft biocompatible material such asnatural or synthetic rubber, Polyester® or other inert/non-allergenic orbiocompatible materials, well known to those skilled in the art. Asshown in FIG. 13, probe tip 400 is cylindrical and may be dimensioned toas to overlie one or more meibomian glands. An alternate embodiment ofprobe tip 400 is shown connected to the handle as illustrated in FIG. 15and in that embodiment is designed to test a larger section of theeyelid to simultaneously evaluate multiple meibomian glands for glandfunction. Probe tip 400 may be press fit, snapped or threaded on to theend of shaft 325.

Per FIG. 14 shaft 325 also includes an annulus 312 proximate the tipmounting end. As shown, shaft 325 is inserted within bore 310 forlongitudinal movement. A helical spring 335 is operatively associatedwith shaft 325 and surrounds a section thereof, biasing the shaft out ofthe housing. Annulus 312 serves as a support or bearing surface forspring 340.

As illustrated in the second embodiment of the invention, shown in FIGS.16-17, the apparatus may also include an indicator means or indicatorgenerally indicated at 408 for indicating when handle 305 has moved thepreselected distance. The indicator means 408 may be selected from thegroup consisting of auditory, visual and tactile signals. Any of thejust mentioned signal means may be employed so long as activationthereof does not significantly impact the force required to move thehandle to ensure that the pressure delivered to the eyelid remains inthe required range. The indicator means 408 comprises a visual indicatormeans or light emitting diode (LED) 405 mounted in end cap 320 such thatthe light emitting portion is at least partially external of the cap andthe electrical leads 410 (schematically shown) extend down into the bore310 and are connected to a battery contact plate 415 also within handle305. A battery 420 is provided proximate the battery contact plate 415.The LED is activated by movement of the handle 305 which causes the endof shaft 325 to complete the electrical circuit and illuminate the LED.Movement of the handle 305 away from the eyelid opens the electricalcircuit and turns off the LED. Circuits of this nature are well knownthe art and a detailed discussion thereof is not deemed necessary.Buzzers, vibrators or other indicator means may also be employed asvisual indicator means.

In the embodiment of FIG. 18, the meibomian gland evaluation tool 300 isgenerally similar to the previously described embodiment except that theshaft 325 is substantially stationary and the means for sensing when thepreselected pressure has been reached comprises a piezo-electric orother similar strain gauge device 440 in combination with anamplification circuit 450 (shown schematically) and which is well knownto those skilled in the art. When the preselected pressure has beenexerted on the eyelid, the amplifier is activated and the indicatormeans 408 is triggered. It is believed that this embodiment will beproduced using molding techniques wherein the cylindrical handle 305will be produced in two longitudinal halves and can be press fittedtogether.

In the embodiment of FIG. 19, the preselected pressure is supplied by aspring means or constant force spring 470 which has a spring constantselected to deliver the preselected pressure to the eyelid. The constantforce spring is coiled and has a connection opening 475 at the outerend. In this embodiment, it is again believed that the handle 305 willbe molded in two opposing longitudinal sections that can be press fittedtogether. One half of handle 305 is provided with upper stop 360 andlower stop 365 in the form of protuberances extending into the bore 310which operate to limit the travel of probe shaft 325, as will bedescribed more fully herein below. In addition, one side of the handleincludes a tang 345 extending from the inner handle wall towards thecenter of the bore 310. The tang 340 should be of a diameter to receivethe opening in the center of constant force spring 470 and should be ofa length sufficient to maintain the spring in place when the two halvesof the handle are connected together. The other end of spring 470 isconnected to a tang 350 located on shaft 325. In the “at rest” state ofthis embodiment, the spring 470 is in the coiled position and tang 350is in contact with upper stop 360. Pressure exerted on the probe tip bymovement of the handle 305 causes the spring to uncoil until tang 350contacts lower stop 365. An indicator means is not provided as theconstant force is delivered merely by unwinding spring 470. Further, itis believed that the clinician will sense when the shaft has reached itsmaximum path of travel when tang 350 contacts lower stop 365, but theindicator means which could buzz, flash, vibrate, or illuminate whenshaft 325 is in the operating range between stops 360 and 365 could alsobe included with this embodiment of the invention.

FIG. 20 illustrates an alternate embodiment wherein the handle shape isrectangular and box-like. Shaft 325 includes a mounting bracket 327 towhich one end of an over center spring or compression spring 480 isconnected. As a compression spring is normally expanded, the first endrests in a cavity or pocket 341 in handle 305. The opposite end ofspring 480 is connected to the bracket 327 by means of a pin or tangformed in the bracket and the shaft is biased in the extended or outwardposition. Pressure on the eyelid acts to compress the spring 480. Whenshaft 325 is pushed such that 327 is past the position of 341, shaft 325will retract away from the eyelid. The device may be reset by pressing areset button 485, as will be appreciated by those skilled in the artupon consideration of the present teachings.

FIG. 21 illustrates another embodiment of the meibomian gland evaluationtool 300 wherein the shaft 325 is connected to handle 305 with acantilever beam 490. A piezoelectric transducer or strain gauge 492together with actuator circuitry identical to that discussed inconnection with the embodiment of FIG. 18. Pressure on probe tip 400causes strain gauge to output a signal proportional to the appliedpressure. When the preselected pressure has been reached, the actuatorcircuit activates LED 495.

In operation, considering for example the device of FIG. 16, theclinician selects the handle 300 having the desired probe tip 400 ormounts the desired probe tip 400 at the end of shaft 325. The probe tip400 is then placed on the external surface of that section of the eyelidto be tested for meibomian gland function. The clinician also equipshimself with the proper equipment (appropriate magnification from a handheld lens, head magnifier, slit lamp, microscope etc.) to be able toobserve the meibomian gland orifice(s). A compressive force in the formof gentle pressure is exerted upon the eyelid by pressing the handle 305towards the eyelid which compresses spring 340. Just prior to the end oftravel shaft 325 makes contact with the battery contact plate 415, theforce of about 15 grams per 30 mm² is reached in a user independentmanner and the clinician observes whether the meibomian gland isproperly secreting or not. The apparatus is designed so that just priorto activation of the indicator means, the cumulative force or energystored in the spring is substantially equivalent to the force requiredfor natural meibomian gland secretion. Of course, the other indicatormeans are actuated in the aforementioned manner as well.

In another embodiment (not shown) of the meibomian gland evaluation tool300, the shaft 325 may be connected to handle 305 which is attached to acoil spring of constant force which rotates and provides force eitherdirectly on the eyelid or by pushing a linear rod attached to the handle305 which applies force on the eyelid.

It will be noted that this apparatus of the present invention may befabricated as a disposable, single use item primarily from plasticmaterials, or alternatively, may be fabricated as a multiple use probewith disposable tips, in which case that portion of the device that isre-used will be fabricated from materials of sufficient durability towithstand repeated autoclaving. Many other variations of such a toolwill occur to those skilled in the art upon consideration of the presentteachings.

Thus, in one embodiment consistent with the present invention a methodof imaging a mammalian meibomian gland of the eyelid involves focusing acamera on a surface of the eyelid containing an orifice of the meibomiangland; from the outer surface of the eyelid, applying adequate pressureto the eyelid to mimic the pressures applied to the meibomian glandduring blinking of the eye, such pressure normally causing fluid withinthe meibomian gland to be expressed and to cause a fully occluded glandto exhibit physical deformities that are observable at the surface; andfrom the outer surface of the eyelid, capturing a diagnostic image ofthe surface of the eyelid.

In certain embodiments, the captured diagnostic image is stored in anelectronic storage medium or displayed on a video display. In certainembodiments, the process further involves treating the occludedmeibomian glands in an attempt to clear the occlusion; and repeating thefocusing, applying pressure and capturing image to capture a posttreatment image to thereby document a degree of success of the treating.In certain embodiments, the diagnostic image is compared with the posttreatment image to determine a degree of effectiveness of the treatment.In certain embodiments, the pressure is applied using an instrument thatapplies a controlled amount of pressure in coordination with capturingthe image. In certain embodiments, the pressure is between approximately10 and 30 grams/30 mm². In certain embodiments, the pressure is appliedusing a hand-held instrument. In certain embodiments, the processfurther involves relating observable conditions in the image withsymptoms of meibomian gland dysfunction to make a diagnosis. In certainembodiments, a proportion of meibomian glands that exhibit symptoms ofcompromised function to make a determination as to a severity ofmeibomian gland dysfunction. In certain embodiments, the proportions ofmeibomian glands that exhibit symptoms of compromised function comprisethose meibomian glands that do not produce clear fluid. In certainembodiments, multiple images are taken of the eyelid in order to imagemultiple meibomian glands. In certain embodiments, multiple images aretaken by a step and repeat action under automated control. In certainembodiments, a computer readable storage medium can store instructionswhich, when executed on a programmed processor, carry out any of theembodiments of the method.

In another embodiment, a method of diagnosing function of a humanmeibomian gland of the eyelid, involves providing a diagnosis decisiontree; focusing a camera on a surface of the eyelid containing an orificeof the meibomian gland; from the outer surface of the eyelid, applyingadequate pressure to the eyelid to mimic the pressures applied to themeibomian gland during blinking of the eye, such pressure normallycausing fluid within the meibomian gland to be expressed and to cause anoccluded gland to exhibit physical deformities that are observable atthe surface; from the outer surface of the eyelid, capturing adiagnostic image of the surface of the eyelid; and relating observableconditions in the image with symptoms of meibomian gland dysfunction tomake the diagnosis. In certain embodiments, the relating involvesdetermining a proportion of meibomian glands that exhibit symptoms ofcompromised function to make a determination as to a severity ofmeibomian gland dysfunction. In certain embodiments, the proportion ofmeibomian glands that exhibit symptoms of compromised function comprisethose meibomian glands that do not produce clear fluid. In certainembodiments, the proportion of glands that exhibit symptoms ofcompromised function comprise glands that secrete fluid that is notclear. In certain embodiments, the proportion of glands that exhibitsymptoms of compromised function comprise glands that secrete no fluid.In certain embodiments, the proportions of glands that exhibit symptomsof compromised function comprise glands that secrete no fluid andexhibit physical deformation at the meibomian gland orifice. In certainembodiments, the captured diagnostic image can be stored in anelectronic storage medium or displayed or rendered on a display orprinted. In certain embodiments, the process further involves treatingthe occluded meibomian glands in an attempt to clear the occlusion; andrepeating the focusing, applying pressure and capturing to capture apost treatment image to thereby document a degree of success of thetreating. In certain embodiments, the pressure is applied using aninstrument that applies a controlled amount of pressure in coordinationwith capturing the image. In certain embodiments, the pressure isapplied using a hand-held instrument. In certain embodiments, thepressure is between approximately 10 and 30 grams/30 mm². In certainembodiments, multiple images are captured under automated control usinga step and repeat process.

In another embodiment, a method of diagnosing function of a humanmeibomian gland of the eyelid involves providing a diagnosis decisiontree; focusing a camera on a surface of the eyelid containing an orificeof the meibomian gland; from the outer surface of the eyelid, applyingadequate pressure to the eyelid to mimic the pressures applied to themeibomian gland during blinking of the eye, such pressure normallycausing fluid within the meibomian gland to be expressed and to cause anoccluded gland to exhibit physical deformities that are observable atthe surface; from the outer surface of the eyelid, capturing adiagnostic image of the surface of the eyelid; rendering the diagnosticimage to a viewable image display medium; relating observable conditionsin the image with symptoms of compromised function by determining aproportion of meibomian glands that exhibit symptoms of compromisedfunction to make a determination as to a severity of meibomian glanddysfunction.

In certain embodiments, the proportion of glands that exhibit symptomsof compromised function comprise glands that secrete fluid that is notclear. In certain embodiments, the proportions of glands that exhibitsymptoms of compromised function comprise glands that secrete no fluid.In certain embodiments, the proportions of glands that exhibit symptomsof compromised function comprise glands that secrete no fluid andexhibit physical deformation at the meibomian gland orifice. In certainembodiments, the method further involves treating the occluded meibomianglands in an attempt to clear the occlusion; and repeating the focusing,applying pressure and capturing to capture a post treatment image tothereby document a degree of success of the treating. In certainembodiments, the pressure is applied using an instrument that applies acontrolled amount of pressure in coordination with capturing the image.In certain embodiments, the pressure is applied using a hand-heldinstrument. In certain embodiments, the pressure is betweenapproximately 10 and 30 grams/30 mm². In certain embodiments, multipleimages are captured under automated control using a step and repeatprocess.

In another embodiment consistent with the present invention, anapparatus for imaging of mammalian meibomian glands of an eyelid,consistent with certain embodiments has an instrument that appliespressure to the eyelid adequate to mimic the pressures applied to themeibomian gland during blinking of the eye, such pressure normallycausing fluid within the meibomian gland to be expressed and to cause anoccluded gland to exhibit physical deformities that are observable atthe surface. A camera focuses on a surface of the eyelid containing anorifice of the meibomian gland, so that the outer surface of the eyelidan image containing the physical deformities of the meibomian glandorifice can be captured when pressure is applied to the eyelid.

In certain embodiments, an image processor receives an output signalfrom the camera and processes the image to thereby electronicallyenhance the image. In certain embodiments, an electronic storage devicestores the captured image. In certain embodiments, a display displaysthe captured image, or a printer or other rendering device renders theimage. In certain embodiments, the instrument is a hand-held instrument.In certain embodiments, the instrument applies a controlled amount ofpressure in coordination with capturing the image. In certainembodiments, the pressure is between approximately 10 and 30 grams/30mm². In certain embodiments, a decision tree provides a reference forcomparison of image characteristics to diagnose the condition of themeibomian glands. In certain embodiments, the decision tree definessymptoms of compromised function to make a determination as to aseverity of meibomian gland dysfunction by determination of a proportionof the meibomian glands exhibiting symptoms of compromised function. Incertain embodiments, a proportion of meibomian glands that exhibitsymptoms of compromised function comprise those meibomian glands that donot produce clear fluid. In certain embodiments, the proportion ofglands that exhibit symptoms of compromised function comprise glandsthat secrete fluid that is not clear. In certain embodiments, theproportions of glands that exhibit symptoms of compromised functioncomprise glands that secrete no fluid. In certain embodiments, theproportions of glands that exhibit symptoms of compromised functioncomprise glands that secrete no fluid and exhibit physical deformationat the meibomian gland orifice.

In another embodiment, an apparatus for imaging of mammalian meibomianglands of an eyelid, has a hand held tool to apply pressure to theeyelid adequate to mimic the pressures applied to the meibomian glandduring blinking of the eye, such pressure normally causing fluid withinthe meibomian gland to be expressed and to cause an occluded gland toexhibit physical deformities that are observable at the surface. Acamera focuses on a surface of the eyelid containing an orifice of themeibomian gland, so that the outer surface of the eyelid an imagecontaining the physical deformities of the meibomian gland orifice canbe captured as an image. A storage device stores the captured image; anda display displays the captured image.

In certain embodiments, an image processor, receives an output signalfrom the camera and processes the image to thereby electronicallyenhance the image. In certain embodiments, the pressure is betweenapproximately 10 and 30 grams/30 mm². In certain embodiments, a decisiontree that defines symptoms of compromised function to make adetermination as to a severity of meibomian gland dysfunction bydetermination of a proportion of the meibomian glands exhibitingsymptoms of compromised function. In certain embodiments, a proportionof meibomian glands that exhibit symptoms of compromised functioncomprise those meibomian glands that do not produce clear fluid. Incertain embodiments, the proportion of glands that exhibit symptoms ofcompromised function comprise glands that secrete fluid that is notclear. In certain embodiments, the proportions of glands that exhibitsymptoms of compromised function comprise glands that secrete no fluid.In certain embodiments, the proportions of glands that exhibit symptomsof compromised function comprise glands that secrete no fluid andexhibit physical deformation at the meibomian gland orifice.

In another embodiment, an apparatus for imaging of mammalian meibomianglands of an eyelid has a hand held tool to apply pressure betweenapproximately 10 and 30 grams/30 mm² to the eyelid adequate to mimic thepressures applied to the meibomian gland during blinking of the eye,such pressure normally causing fluid within the meibomian gland to beexpressed and to cause an occluded gland to exhibit physical deformitiesthat are observable at the surface. A camera focuses on a surface of theeyelid containing an orifice of the meibomian gland, so that from theouter surface of the eyelid an image containing the physical deformitiesof the meibomian gland orifice can be captured. A storage device storesthe captured image and a display displays the captured image; an imageprocessor, receives an output signal from the camera and processes theimage to thereby electronically enhance the image.

In certain embodiments, a decision tree defines symptoms of compromisedfunction to make a determination as to a severity of meibomian glanddysfunction by determination of a proportion of the meibomian glandsexhibiting symptoms of compromised function. In certain embodiments, aproportion of meibomian glands that exhibit symptoms of compromisedfunction comprise those meibomian glands that do not produce clearfluid, glands that secrete fluid that is not clear, glands that secreteno fluid and glands that both secrete no fluid and exhibit physicaldeformation at the meibomian gland orifice.

NIR Imaging

NIR optical imaging is an extension of visual light imaging, where thesample is illuminated with Near Infra Red (NIR) light (about 0.650-2.5microns), either transmitted through the object, or reflected from theobject, and the light is focused onto a typical red sensitive CCD camera(out to about 1.2 microns) to produce a monochromatic image. Theseimages show the spatial resolution of structures, not the temperatureprofile. The spatial resolution of these images is proportional to thewavelength of light, so an image taken with 1 micron (NIR) wavelengthlight will have half the resolution of an image taken with 0.5 micronwavelength (green) light, all other things being equal (for example).Penetration depths in human tissue of the IR illumination can vary within the range of a few mm to a few cm.

NIR optical imaging can be accomplished using a suitable infrared lightsource and highly sensitive CCD (charge-couple device) camera thatrecords light reflected from the eyelid. For example, NIR light from atungsten-halogen bulb penetrates human tissue to a depth adequate toilluminate the meibomian glands. A portion of the light travelingthrough human tissue is absorbed by chromophores, or light-absorbingmolecules, in the skin's layers. By beaming light onto the patient'seyelids and measuring reflected light, differences between lightreflected by chromophores and other body tissues and the fluid and/ortissue of the meibomian glands can be visualized.

NIR cameras are readily available and have a penetration depth more thanenough to see through eyelids. By use of optics of a typical slit lampmicroscope that are able to pass NIR frequencies (and are suitablymodified if necessary to pass NIR frequencies), NIR cameras can be usedto image the meibomian glands. Illumination with NIR lighting can beeither from behind the eyelid for transmission, or in front of theeyelid as illustrated below for reflected light imaging.

Near Infrared imaging can be utilized to ascertain the condition andfunction of the meibomian glands as depicted in FIG. 22. NIR cameras,and in particular high resolution NIR photography, can be used to imagethe eyelid to some depth inside the tissue. The blood vessels located inthe eyelid will be denser in areas outside the meibomian glands and theglands themselves will be filled with material which will have adifferent NIR response than the surrounding tissue. Using a HighResolution NIR camera should result in the ability to differentiatebetween the various tissue, the glands and material causing occlusion ofthe gland orifice.

In NIR imaging, the eyelids can be imaged using near infraredphotography techniques, generally in approximately the 0.650 to 2.50micron wavelength to detect differences in the transmission orreflection of infrared light from the meibomian glands. This is incomparison to the approximately the 3-8 micron wavelength used in nightvision infrared imaging, where thermal radiation from the body is theimaging energy.

In this process, a near infrared (NIR) camera 500 is used in conjunctionwith a NIR light source 502, through suitable magnification representedby 504, to capture an image of the eyelid (e.g., lower eyelid 24) andassociated meibomian gland 20. The camera 500 may produce conventionaloptical photographic images that can either be developed and viewed orcan be directed to an image processing computer 208 that can thenprocess and possibly enhance (e.g., by use of pseudo-color colorassignment techniques to assign different colors or color ranges todifferent fray levels emitted from the target image) the image. Theimage can then either be displayed on a display monitor 212, or storedon disk or other storage 210, or printed on a photographic qualityprinter 216 or any or all of the above. In addition to still NIR images,moving NIR images can similarly be captured in this manner to produce,for example, a pan across the eyelid in which individual frames can becaptured and printed if desired.

In accordance with certain embodiments consistent with the presentinvention, the NIR camera may be based upon readily available highresolution NIR cameras. Either a conventional lens can be used withmultiple images taken to image various areas of the eyelid, or aspecially designed lens can be provided which provides for focus on thecurved surface of the eye, and thereby compensate for the curvature ofthe eye.

An NIR camera can be utilized to image the eyelid to some depth insidethe tissue. The blood vessels located in the eyelid will be denser inareas outside the Meibomian glands and the glands themselves will befilled with material which will have a different NIR response than thetissue around it. A High Resolution NIR camera should be able todifferentiate between areas of tissue and areas of glands. Thewavelength and optics used for the NIR camera should be selected toprovide suitable imaging of the meibomian glands and can be optimized byexperimentation. Additionally, it may be advantageous to digitallyprocess the resulting images to enhance the contrast level and/or assigncoloration to distinguish between the NIR responses of the varioustissues.

In addition to the NIR photography technique using a slit lampmicroscope, imaging can be carried out using a suitable microscopicobjective lens. As noted previously, the central duct of a meibomiangland is on the order of about 100 microns in diameter. Additionally,the glands are separated by approximately 1 mm and have an orifice onthe order of approximately 0.1 mm (based upon a limited sampling ofhuman subjects). The orifice is closed when not secreting—the size ofthe orifice of approximately 0.1 mm is obtained by placing pressure onthe gland to open the orifice and then making the estimation of the 0.1mm size. The TABLE 1 below shows the resolution of objective lenses forlight at 900 nm (0.9 microns) wavelength. Based upon these data, amicroscopic objective lens having between about 60× and 10×magnification should be suitable for providing high resolution imagingof a meibomian gland. The field of view listed in TABLE 1 refers to thediameter of the viewable area of the sample.

TABLE 1 Objective 63X 40X 20X 10X 5X 2.5X Numerical 1.32 0.75 0.5 0.30.15 0.075 Aperture Resolution 0.42 0.73 1.10 1.83 3.66 7.32 (microns)Field of 317 500 1000 2000 4000 8000 View (microns)

It should be noted that if one wished to see the total lid of 30 mm, afield of view of about 30,000 mm would be needed—consider in view oflegal considerations. It is further noted that the total imagemagnification can increased by a factor of 10× with a 10× eyepiece onthe microscope, however the resolution is determined by the objectivelens.

In certain embodiments, the NIR camera has an objective lensmagnification of between about 60× and 10× between about 650 and 900 nmwavelength. As an example the range of 16× to 25× is the most commonrange used with a slit lamp for imaging one or several glands. However,it would also be desirable to image the entire lid to see the generalcharacteristics of all of the meibomian glands. This can be performed inthe range of 10× to 16×. Also, if imaged on a video screen consider themagnification assume the lid is 30 mm wide=1.2 inches—One could only use10× to see the entire lower lid if the screen were 12″. Thus extendmagnifications to preferred 10× to 25×, and range as great as you decidewould not compromise patent—60 is on the high side since the use of anymagnification over 25 and certainly 40× is difficult because ofexaggeration of movement. In certain embodiments, the imaging is carriedout using NIR optical imaging approximately in the 0.650 to 2.5 micronwavelength range. In certain embodiments, the imaging is carried outusing trans-illumination photography. In certain embodiments, thetrans-illumination is produced by oblique illumination of the eyelidfrom an anterior surface thereof. In certain embodiments, thetrans-illumination is produced by lighting the eyelid from a posteriorsurface thereof. In certain embodiments, the trans-illumination isproduced by use of a scleral lens serving as a light source from theposterior surface of the eyelid. In certain embodiments, thetrans-illuminating is carried out using a lenspiece comprises an arrayof light emitting elements mounted to a substrate suitable for contactwith eyeball. In certain embodiments, the NIR radiation includesradiation having wavelength that is either absorbed or transmittedpreferentially through lipid rich material versus tissue surroundinglipid rich tissue. In certain embodiments, at least one of the imagingand re-imaging is carried out while pressure is applied to the eyelidthat simulates an amount of pressure caused by blinking the eyelid.

Thus, a method of near infrared (NIR) imaging of a meibomian glandinvolves illuminating the meibomian glands with NIR radiation using anNIR light source; focusing an NIR camera on a region of an eyelidcontaining the meibomian gland; making a first NIR image of themeibomian gland; applying a pressure suitable for simulating blinkingpressure on the meibomian gland; optionally refocusing the NIR camera onthe region of the eyelid containing the meibomian gland; and making asecond NIR image of the meibomian gland while the pressure is beingapplied. The method is preferably carried out with the NIR camera havingan objective of between about 60× and 10× between about 650 and 900 nmwavelength. Light emitting diodes (LEDs) producing light in or aboutthis range may provide useful sources for illumination, and some leewayshould be provided to account for the limited spectrum that can beproduced by LEDs.

FIG. 23 depicts an exemplary image that might be obtained via opticalnear infrared photography. In this image, simplified for purposes ofthis illustration to demonstrate only anatomical features of interest,it is expected that an image of an occluded meibomian gland willtransmit IR radiation at differing intensities at the location of theoccluded orifice 30 (at 34) and the occluded acini 29 (at 36) than wouldbe expected at a normally functioning gland. Thus, the image can beprocessed to present a different density or color of the image atorifice 30 and occlusion 34 and acini 29, central duct 28 and occlusion36 than of the remainder of gland 20 and surrounding tissue of theeyelid 24. Note that while FIG. 23 illustrates a single meibomian gland,this is for illustrative purposes only since one, more or all of theglands or the entire eyelid or both eyelids may be imaged in a singleimage or multiple images in various embodiments.

FIG. 24 depicts an exemplary process 530 for imaging the meibomianglands using near infrared photography in a manner consistent withcertain embodiments of the present invention starting at 534 after whichthe NIR camera is focused on the surface of the eyelid (or on the MGwhere possible). (For other imaging techniques, analogous processes canbe utilized with suitable modification e.g., using a visible lightcamera or ultrasound device rather than an IR camera.) An image is thencreated at 542 to create a pre-treatment reference image. This image maybe processed as described above, either by fully automated means of withthe assistance of manual intervention to highlight significantattributes by color assignment or enhancement. The glands may then betreated using any suitable treatment mechanism at 546. The effectivenessof the treatment can then be evaluated by imaging the eyelid in the samemanner as previously by refocusing the IR camera on the eyelid at 550and re-imaging the eyelid using infra-red photography and enhancement asneeded at 554. The process ends at 560. As has been previouslydiscussed, the application of pressure may also be used during theimaging process to augment the process and determine the state offunction of the glands. Either still or moving images may be used in theimaging process, and pressure can be applied as described above to mimicblinking pressures.

As noted above, in one embodiment, the IR camera may be fitted with alens designed to correct for the curvature of the human eye. While thereis variation in the size and curvature of the human eye, a lens designedfor the average can likely be used across the spectrum of eye sizes withadequate performance.

As is the case with any microscopic imaging process, the image shouldpreferably be produced under circumstances wherein the object beingimaged is as stable as possible. In this case, the head can bestabilized in a conventional manner using conventional ophthalmologicchin and forehead braces as are used in conventional ophthalmologicexams, with the examination braces fitted with suitable infraredphotography instruments as described above.

Trans-Illumination

A new form of trans-illumination can be used to image the meibomianglands in one of several ways. In one variation illuminating light canbe directed at the outer anterior surface of the eyelid at an angle,with imaging also taking place from the outer anterior surface of theeyelid. This is referred to as oblique illumination. In a secondvariation, light can be directed from behind the eyelid through theeyelid with imaging taking place through the outer surface of theeyelid. In a third variation, the surface is illuminated from the frontin a manner such that the light source partially blocks the image beingrecorded, with averaging, adding or otherwise combining of multipleimages being used to produce a complete image. In each instance, themeibomian gland is illuminated in order to visually examine the glandusing light transmitted through the eyelid tissue. The eyelid can thenbe imaged using still or moving photography (visible light, NIR or IR orother suitable light wavelength) in a manner similar to that depictedabove.

The first variation of this technique is depicted in FIGS. 25-26. Withreference first to FIG. 25 the basic concept of obliquetrans-illumination for imaging the eyelid and associated glands isdepicted. In this illustration, light is directed toward the eyelid at asuitable angle to cause a section of the flesh of the eyelid to betrans-illuminated by transmission of light through the flesh itself. Inthis case, a light source 604 is simply depicted as a light conductingfiber that directs light to a desired location of the outer surface ofthe eyelid. The light can be of any suitable wavelength including nearIR radiation. A light receiving element (which again is depicted as anoptical fiber) 608 is positioned on the same outer surface of the eyelidin order to image the trans-illuminated area of the eyelid and one ormore meibomian glands such as 20. In certain embodiments, this techniquecan be used to completely manually probe the eyelid as with the manualprobe depicted in FIG. 26, while in other embodiments; the eyelid can bescanned by moving the probe (light source and receiver) in an organizedmanner (e.g., under computer control) over the eyelid and electronicallyassembling a larger image of the eyelid.

In accordance with various embodiments, the source fiber 604 and thereceiver fiber 608 can be individually manipulated, or may be containedin a single hand-held probe 634 as depicted in FIG. 26. In such a probe,both fibers can be optically isolated and stress relieved in a singlecable 638 that is attached to a combined light source 612 and opticalreceiver unit 616 as shown separately in FIG. 27. The tips of the probecan be of such design as to capture the image of a small (e.g.,approximately circular, oblong, rectangular, etc.) region of the eyelidusing a single imaging element or a small array of imaging elements(e.g., CCDs), or a vertical or horizontal stripe of the eyelid so as tocapture the length of an individual or set of meibomian glands by usinga rectangular array of imaging elements, or any other suitable array ofelements. Additionally, a full or partial image of the eyelid can beassembled electronically by stitching, adding, averaging or otherwiseelectronically combining overlapping images using photographic stitchingor combining techniques. The imaging element or elements should bematched to the wavelength of light that is to be captured. In certainembodiments, NIR radiation is used and hence, the imaging elements canbe suitable for receipt of light in the NIR spectrum.

FIG. 27 depicts a more complete image of the imaging setup in whichfiber 604 directs light from a suitable light source such as a lightemitting diode, laser, NIR source, incandescent or halogen source 612 tothe eyelid. The resulting image is received via light conduit 608 thatis matched to the light source at an optical receiver 616 (also matchedto the light source) which delivers a digital representation of theimage to a processor such as a microcomputer 620 having associatedworking memory 624 and mass storage such as disc drive storage 210. Theimage can be stored at storage 210 for later retrieval, processing orenhancement. The image can also be viewed in real time or at a latertime on display 212, or can be printed on printer 216, each of which isconnected to the processor 620 via a suitable display and/or printerinterface 630.

In certain embodiments, as described previously, the light source andoptical receiver can be moved across the eyelid in an organized mannerusing an X-Y (or X-Y-Z) controller and a suitable servo motorarrangement (not shown in this illustration) under control of theprocessor 620 in order to scan a larger surface. Scanning the eyelid canbe accomplished manually or by use of an X-Y control system asillustrated. In such an embodiment, the light source 612 and opticalreceiver 616 may be scanned across the eyelid in a suitable pattern toproduce a full X-Y scan under control of X-Y scan controller 658 drivinga servo arrangement 662, while high resolution camera 650 records theresults.

In another variation of the trans-illumination technique, depicted inFIG. 28, a device similar to a contact lens or scleral lens 640 istemporarily placed in the eye to act as a source of light that is fed bylight source 612 via fiber 604. Fiber 604 is shown as illuminating thelens at an edge, but could also illuminate the lens near the center orfrom multiple locations without limitation in order to shine lightthrough the eyelid from behind. The light can be of any suitablefrequency matched to the imaging process, including white light or NIRradiation. This contact lens 640 can resemble a small eye shield similarto a scleral lens. A high resolution camera 650 can then be used toimage the eyelid or the eyelid can be observed during illuminationthrough a slit lamp microscope. Preferably, the contact lens has areflective back side to protect the eye from exposure to high intensitylight, coupled to a frosted lens element that scatters the lightdirected thereto by the light fiber 604 which is optically coupled tothe frosted lens element or other dispersive arrangement such that thelight of desired wavelength is scattered throughout the lens. Multiplesizes of the lens can be provided to approximately accommodate eyes ofvarious sizes, but need not be a perfect fit since the duration of needfor installation of the lens against the eye is short term, and shouldresult in minimal discomfort. Local anesthetic can also be used tominimize discomfort.

The lens 640 is illuminated by light of the desired wavelength (e.g.,NIR or visible) passing through fiber 604 so that light is therebypassed from the posterior surface of the eyelid through the eyeliditself to illuminate the interior surface of the eyelid for imaging.This produces an image of the interior of the eyelid that can becaptured in much the same manner as an image produced by shining abright flashlight through a human hand (wherein, bones are readilyvisible through the flesh). Light of various colors or colorcombinations (including visible, UV, IR, NIR or combinations thereof)can be used in this embodiment.

Therefore, the present trans-illumination techniques can provide moreconsistent results with greater patient comfort than the technique incurrent use. In addition, automatic image capture and analysis can beincorporated. In this embodiment, a light source built into a small eyeshield 640 similar to a scleral lens as described above provides theillumination source without providing a significant amount of heat. Thenhigh resolution camera 650 is used to visualize the resulting image.Various techniques can be used to increase the signal to noise ratiounder low light conditions. Some of these techniques can produce motionartifacts in the image that should be noted in considering or imageprocessing the output image. Image processing can be utilized tominimize such artifacts.

In a third alternative embodiment, as depicted in FIG. 29, an LED lightsource (or other suitable light source or light conduit therefrom suchas a NIR light source) 654 can be placed close to or in contact with theoutside of the eyelid (e.g., 24). The light source 654 is then manuallyor automatically scanned across the eyelid in a suitable pattern toproduce a full X-Y scan under control of X-Y scan controller 658 drivinga servo arrangement 662, while high resolution camera 650 records theresults. The various image frames taken during the scan are thencombined (e.g., stitched, averaged or added) together at processor 620resulting in a composite trans-illuminated image. Alternately, the imageof the light source can be subtracted from the resulting images. Thetheory behind this technique is similar to shining a flashlight on yourhand and looking at the hand from the same surface as the light sourceis illuminating. You can see the tissue around the flashlight but youcannot see through the flashlight itself because it is blocking yourfield of view. However, if you move the flashlight around and recordimages at many positions, it is then possible to eliminate theflashlight body from your image by combining all of the resulting imagestogether. Further image processing may also be carried out to enhancethe resultant image. For example, in one embodiment, image recognitiontechniques can be used to recognize the shape of light source 654, andsubtract that image from each image. Data from other images can then beinserted into the image from which the light source is subtracted. Theprocess may be potentially further enhanced by experimentation withvarious illumination wavelengths.

In the above example, light is provided directly in front of the camera,while in prior examples, light was provided at the side of the camera orbehind the eyelid. Hence, it will be evident that the light source canbe placed in any suitable location with respect to the eyelid and thecamera in order to produce trans-illumination of the meibomian gland orglands without limitation.

Referring now to FIG. 30, another embodiment of a trans-illuminationapparatus is depicted schematically which can provide not only a highlevel of light transmission through the eyelid, but also can havetherapeutic benefits of providing heat. In this embodiment, an array oflight sources such as Light Emitting Diodes (LEDs) 680 are arranged on alight array assembly 684 which is then mounted to a lenspiece (e.g.,again resembling a scleral lens) that is placed in contact with the eyeand the eyelid covering the assembly. Wiring then passes through asuitable type of wiring harness mechanism (wires or a connector of anysuitable design) to a power source (e.g., voltage or current source) 690that forms a part of a controller device 692. In this embodiment, powersource 690 operates under control of control processor 694 to supply acontrolled suitable combination of current and voltage to the lightarray assembly to produce the desired illumination. The power source maybe current limited or may include a series resistance or use othertechniques to assure that the LEDs are not damaged by excess current.

In addition to providing a high level of trans-illumination, the presentapparatus further provides heating of the tissue of the eyelid, whichhas been found to be therapeutic in melting or otherwise relievingocclusions of the meibomian glands and other abnormalities of the eyeand eyelid. Since LEDs are generally about 5-7% efficient in generationof light, and the remainder of the power sent to the LED array 680 isconverted to heat, the trans-illumination can accompany heat generationand therapy. U.S. Provisional Patent Application No. 60/880,850 filedJan. 17, 2007 describes a device in which heating elements are used as apart of a scleral lens-like assembly, and the present light arrayassembly can serve the purpose of the heating elements described in thatapplication and may further provide the desired trans-illuminationeffect discussed above.

Since the light array assembly 684 is used in intimate contact with eyesand may carry a risk of contamination if reused, it is desirable thatthe assembly 684 is configured to be a one-time use assembly. In orderto facilitate this, it is further desirable that the assembly bedisabled so as to discourage further use once the device has served itspurpose on a single patient, thereby providing protection againsttransmission of disease. Hence, in one embodiment, a fusible link isprovided in the path that supplies power to the LED array 680. At theend of a treatment or diagnosis cycle, the control processor 694 canclose a switch 698 in order to intentionally blow the fusible link 696rendering the light array assembly inoperative. In certain embodiments,the fusible link may be realized by providing a narrow segment of a flexcircuit trace that is inherently less capable of carrying higher levelsof current than a larger trace. In other embodiments, a separate circuitelement may be used.

In some embodiments, blowing the link can be accomplished as shown withgrounding the LED array 680 side of the fusible link 696 so thatpositive current flow is shorted to ground directly through the linkbypassing the LED array 680. In such a configuration, it may also bedesirable to provide a diode in the path toward ground (toward theswitch) in the light array assembly to assure that power cannot besupplied surreptitiously to the light array assembly in a path thatbypasses the fusible link without considerable difficulty and rework.While three contacts or connections between the control unit 692 areshown, other connections can also be provided in order to permit thecontrol processor to monitor temperature or carry out other functions,as will be appreciated upon consideration of the teachings of the aboveProvisional Patent Application.

The process just described is presented as process 700 of shown in theflow chart of FIG. 31 starting at 704. The processor 694 instructs theheating and/or illumination device 684 to operate through a cycle ofillumination and/or heating actions in any suitable manner at 708. Oncethe cycle of heat treating or illuminating is completed at 712, theprocessor 694 closes switch 698 in order to burn out fusible link 694(or takes any other suitable action to disable the light array assemblethereby preventing reuse) and the process ends at 720.

FIG. 32 depicts the physical and mechanical configuration of the lightarray assembly 684 in accord with one embodiment. In this embodiment,the lenspiece 724 resembling a scleral lens in shape (i.e., somewhathollow dome shaped) is designed to fit over the eyeball on the concaveside and is configured to carry LED array 680 on the convex side. TheLED array 680 is configured to provide a sub-array adjacent the lowereyelid margin and a sub-array adjacent the upper eyelid margin asdepicted as 680A and 680B respectively. A male connector member 728extends outward approximately normal to an approximately centralizedarea of the convex surface of lenspiece 724 and provides an array ofelectrical contacts 732 that can be connected to a female electricalconnector 734. In this embodiment, the female connector 734 isconfigured to receive the male connector member 728 and clamp to it byengaging a flexible snap-together portion 738 with a contact portion 742that carries pins or other contacts that electrically engage the contactarray 732. The connector provides an electrical cable that iselectrically connected to the contact portion in order to send andreceive electrical signals to the light array assembly 684. Desirably,connection should be made to the male connector member without applyingsignificant pressure to the eyeball through the lenspiece.

FIG. 33 depicts a flex circuit 750 (i.e., a thin, flexible substratecarrying circuit traces and electronic components) that is used incertain embodiments to realize a portion of the light array assembly684. The flex circuit 750 depicted has an array of surface mounted LEDelements that form sub-arrays 680A and 680B. These sub-arrays form theLED array 680 and can be electrically configured in any suitable seriesand/or parallel configuration to permit application of power to thearray so as to create the desired illumination. The flex circuit 750also carries the array of electrical contacts 632 that are used tointerconnect with the LED array 680. For clarity, no particularelectrical connection is specifically shown, since any suitable seriesand/or parallel arrangement can be used if appropriately supplied withpower. The flex circuit can also be provided with other electroniccircuit elements as desired to carry out other functions, includingtemperature monitoring and fusible link. The fusible link can befabricated by making a narrow trace on the flex circuit.

The dashed lines 754 depict folds or creases that are made in the flexcircuit in order to mount the flex circuit 750 to the lenspiece assembly684. This is further depicted in FIG. 34 which illustrates the foldsmade in flex circuit 750 to conform to the shape of male connectormember 728 and eyepiece 724. Once the folds are made, the flex circuit750 can be bonded to the eyepiece 724 and the connector member 728 usingany suitable adhesive mechanism. Since the surface mount LEDs that formLED array 680 protrude above the surface of the flex circuit 750, theymay provide a rough edge that will be uncomfortable to the wearer. Inorder to minimize this, an over-molding or coating, for example of aplastic, or other coating designed to smooth the surface can be appliedto the assembly to make the outer surface thereof smoother. Thethickness that can be tolerated with reasonable comfort for shortperiods of time by a human subject of such a light array assembly issurprisingly thick. The approximate thickness of the embodiment ofassembly 684 depicted that is placed between the eye and the eyelid canbe between about 0.5 mm and about 6 mm and should be readily toleratedfor short time periods by human subjects. The 6 mm upper limit of therange is possible for many, but at upper limit for most eyes is moredesirably in the range of up to 3.5 mm.

FIG. 35 depicts another embodiment of the light array assembly depictedgenerally as 770 which is functionally equivalent to assembly 684 andinterchangeable therewith. In this embodiment, the lenspiece has a flexcircuit similar to 750 applied to a convex surface thereof, but does notincorporate a connector member 728. Instead, wires 746 are directlyattached to the flex circuit and are connected using any suitableconnection method (e.g., soldering or conductive adhesive connection) tothe control unit 692. A connector may advantageously interposed betweenassembly 770 and the control unit to facilitate reuse of the controlunit and disposal of assembly 770. In accordance with this embodiment,the central portion of the flex circuit 750 is shortened as comparedwith the circuit shown on FIG. 33, and provided with contact areas fordirect connection to the wires 746.

In this embodiment, the lenspiece is preferably opaque to protect theeyeball from the highly intense light of the light array assembly.Additionally, the flex circuit is preferably white or reflective toassist in providing a uniform light source. The coating should bebiologically acceptable for placement between the eyeball and eyelid andmay be tailored to provide multiple purposes. In addition to providing asmoother surface for contact with the sensitive underside of the eyelid,it can provide light scattering properties by being translucent orotherwise diffusive, or may provide color filtering properties ifdesirable, or may be clear for maximum light transfer without departingfrom embodiments consistent with the present invention.

U.S. Provisional Patent Application No. 60/880,850 filed Jan. 17, 2007describes a heat treatment apparatus for treatment of the eye. Theassembly of FIG. 32 above can be adapted for use as a treatment devicein the same manner as that of the provisional application as illustratedin FIG. 36 by addition of an eye shield or eyecup 780 and a fluidbladder 784 which provides for mechanical manipulation of the eyelid inorder to assist in expressing melted obstructive material from themeibomian glands. In this case, the light producing devices also produceheat, and by regulating that heat, the heater assembly as shown in theprovisional application, in all embodiments, is simply substituted withthe light array assembly. In such embodiments where the light sourcealso provides (or is provided as a part of) a heat source, the eyepieceserves as an insulator that prevents the heat treatment from and amechanism is provided for applying pressure to the eyelid or lenspiece724.

In the most basic form, lenspiece/insulator 684 is concave in shape onthe eyeball side and mirrors the curvature of the eyeball, substantiallysimilar to a contact lens. As employed herein, the term “insulator” isintended to include any component or material wherein there is greaterresistance to thermal conduction or radiation towards the surface of theeye than towards the eyelid. Stated alternatively, in the insulatorthermal energy radiates more easily towards the eyelid than towards theeyeball surface in order to minimize the possibility of causing injuryto the eyeball. In a model that supplied heating alone, the diameter wassufficient to more than cover the cornea or in the approximate range of15 mm to 25 mm would be sufficient for most eyes assuming a cornealrelief zone of approximately 16 mm. It will be noted however, that thediameter of the insulator can vary beyond the ranges stated above.Further, the lenspiece 684 is constructed from a biocompatible materialsuch as polymethylmethacrylate (PMMA) or in the case of the prototypethat was constructed, epoxy or other materials well known to thoseskilled in the art. The insulator may be flexible, but ideally should beonly minimally compressible, as will become clear from the discussionthat follows.

According to certain embodiments of the invention, the lenspieceinsulator 684 is inserted on the surface of the eye, behind the rearsurface of the eyelid and should include smooth edges so as not toscratch or cut either the eyelid or the eye. As used herein the term“eyelid” or “eyelids” is intended to include the upper lid and the lowerlid, either in singly or in combination. The insulator provides a backplate against which pressure may be applied. In limited circumstanceswhen the obstruction in the meibomian gland channel is minimal, themeibomian gland may be cleared merely through the application ofpressure externally applied to the eyelid, such as gentle fingerpressure. More specifically, with the insulator in place behind theeyelid, finger pressure is applied to the external surface of theeyelid, the eyelid being sandwiched between the finger and theinsulator.

In other instances, the meibomian gland obstruction may be blocked to adegree greater than can be treated with simple pressure alone. In suchcases it is necessary to apply thermal energy to the eyelid in order toloosen, break up, fracture, soften or liquefy at least a portion of theocclusion. Thermal energy may be applied by any one of the well knownmeans for applying thermal energy such as modalities such as resistive,IR (infrared), ultrasonic heating, microwave, any one of the numerous“hot pads” that chemically produce an exothermic reaction or in thesimplest form a hot compress. In the present embodiment, at least aportion of the heat may be provided by the excess heat generated in theLEDs. Experimentation has revealed that in order to be clinicallyeffective the eyelid should be heated to a temperature of between about35 degrees Celsius and 47 degrees Celsius. The length of time for whichthermal energy, i.e., heat is applied to the eyelid depends upon theextent that the obstruction blocks the meibomian gland channel as wellas the composition of the obstruction. In very minor cases, heat may beapplied to the eyelid for less than three minutes or even as little asfive to fifteen seconds. On the other hand, extreme blockage may requireas much as thirty minutes of heating to soften the obstruction prior tothe application of pressure to the eyelid to express the softenedobstruction.

Experimentation has further revealed that the eyelids are efficient heatexchangers with circulating blood acting as the cooling mechanism andthat the eyelid temperature returns to normal in less than two minutesat which time the obstruction re-hardens making extraction difficult. Itis therefore necessary to apply the aforesaid expressive force to theeyelid within that time frame in order for the treatment to besuccessful. Thus, gentle finger pressure, preferably in a milking typeaction, to urge the obstruction upward and out of the meibomian glandorifice should be employed. Again, depending on the nature and locationof the obstruction, mere compressive force may be effective in someinstances.

In a further embodiment, the insulator is inserted between the rear ofthe eyelid on the surface of the eyeball as previously described. Aneyecup 780 is employed to provide pressure to the eyelid. In oneembodiment, thermal energy is applied as described above, an eyecup 780(which may be unheated) is placed on the outer surfaces of the eyelidand pressure is applied thereto to express the softened obstruction. Theeyecup minors the size and shape of the eyelids when closed.

Eyecup 780 is adapted to overlie the outer surface of the eyelid,substantially conforms to the surface shape thereof and is adapted tocooperate with the lenspiece insulator 724. Eyecup 780 includes acentrally located longitudinal slot which receives the male connectormember 728. In certain embodiments, positioned on the underside of theeyecup 780 is a diaphragm arrangement as described in the provisionalapplication and shown as 784. The pair of diaphragms 784 are in fluidcommunication with each other and include an inlet or inlet. Diaphragms784 are attached to the eyecup 780 via conventional means such as glue(not shown). It will be noted that the eyecup could be provided with asingle diaphragm with a hole defining an opening through male connectormember 728 may pass.

Diaphragms 784 may be fabricated from a biocompatible material such aspolyurethane foam (open or closed cell), a sealed air balloon, agel-filled bladder. Again, depending upon the type and degree ofobstruction, the diaphragms will vary in thickness and/or durometer. Inan alternate embodiment, diaphragms 784 may comprise bladders which maybe fabricated from any flexible expandable material such as rubber orplastic, however, it is preferred that the coefficient of expansion belinear with respect to the amount of fluid added. The bladders may bepartially filled with a constant amount of fluid or they may be providedwith a rudimentary pump connected to inlet 305 such as is used with aperfume aerosolizer. The fluid is preferably air, but may also be aliquid such as water, saline, etc. Further, while not shown, the fluidmay also be heated in order to assist in the softening of any meibomiangland obstructions which may be present. It will be noted that for anygiven patient, the either or both of the insulator and fluid may beheated as required in order to soften any given obstructed meibomianglands. While not illustrated, the bladders could be fabricated in sucha manner that as they inflate pressure is applied which urges thesoftened gland obstructive material up the gland channel and out of thegland orifice to clear the gland. One method would be to increase thethickness of the bladders such that there is less resistance (lessthickness) to inflation near the bottom of the gland and the resistanceincreases (greater thickness) as one reaches the gland orifice.

In operation, the lenspiece insulator 724 is placed on the sclera of theeye in much the same manner as a contact lens is inserted. The eyecup780 and bladder 784 are then positioned with the concavity facing theeyelid. The connector 734 is then used to couple lenspiece 724 to theeyecup 780. Heat is then activated by a switch or control processor 692or other means to which the heated fluid in the bladders 784 may beadded simultaneously or serially for the preselected period of time, forexample, two minutes. Thereafter, or simultaneously with the applicationof heat the bladders 784 may be expanded which will urge the softenedmeibomian gland sebum up and out of the gland channel towards the glandorifice, thus, unblocking the gland. When treatment is complete, theconnector 734 is disengaged and the lenspiece 724 and bladders 784 areremoved. The assembly 684 can then be readily removed from the eyeballand treatment is complete.

It will be noted that various mechanisms to lock the insulator to theeyecup could be employed such as a ratchet type mechanism, a press fitas well as other mechanisms well known to those skilled in the art, notdiscussed herein. While not specifically required, it is preferable thatthe locking mechanisms be near “zero insertion” force in order tominimize the potential for eye injury.

Yet a further embodiment of a tool for use in trans-illumination of theeyelid is depicted in FIG. 37. In this embodiment, the device 800 ismanually manipulated by a physician, technician, etc. to provideillumination to an isolated portion of the eyelid. In this embodiment, asmall paddle-like eye shield 806 provides a surface for mounting of theLEDs in LED array. The eye shield is opaque to permit light to shineonly toward the inner surface of the eyelid while shielding the eye fromthe bright light. The paddle-like eye shield is mounted to the end of ahandle 810 that serves as a battery holder that can hold severalbatteries used to power the LEDs, in which case an end cap 814 may beremoved to access the batteries in the manner of a flashlight, or mayserve to couple externally supplied power to the LEDs.

In use, the eyelid is lifted away from the eyeball and the paddle isinserted between the eyelid and the eyeball pulling the eyelid outwardto trans-illuminate a portion of the eyelid. Additionally, thepaddle-like eye shield can be used as a surface against which to applypressure through the eyelid to express fluid from the meibomian glandsor abnormal structures of the eye such as a stye, pimple, chalazion andhordeolum or other abnormalities that can be treated by heat, pressure,light or release of trapped fluids. This pressure can be applied usingthe tool depicted in FIGS. 13-21 or by use of a finger or other tool.

Once trans-illuminated, by any of the methods depicted, the meibomianglands or other eyelid structures can be visualized or imaged using anyof the arrangements previously described. Any motion artifacts should beconsidered in evaluation of the images, or processed out of the images.

As described above, NIR imaging can be carried out by use oftrans-illumination techniques as described above. This technique can becarried out by use of a light source placed behind the eyelid. In theembodiment described above, this light source takes the form of ascleral lens 640 that receives light from a source, such as a NIR lightsource, and directs light outward through the eyelid to facilitatevisual or photographic observation of the condition of the meibomianglands. This observation can be made by either microscopy or microscopicphotography.

U.S. Provisional patent application No. 60/880,850 filed Jan. 17, 2007describes a device that uses a heated lenspiece (i.e., a deviceresembling a scleral lens in that it is placed in contact with theeyeball between the eyeball and the eyelid) which is placed behind theeyelid and is used for treatment of the eyelids for MGD. In anotherembodiment, this device can be adapted to use a similarly configuredlenspiece, but replaces the heater element with a light source to enabletrans-illumination of the eyelid while the eyelid remains in its normalposition. This light source can be designed to provide illuminationusing visible light, IR light, NIR light, UV light or any combinationthereof that is found suitable for visualization of the MG structures orother features of the eyelid.

In order to provide manual trans-illumination to visualize the vesselsand glands within the eyelid, a great deal of skill and dexterity isnormally required on the part of the physician. In the conventionaltechnique, the eyelid is manipulated around the light source to providelighting from the outer surface of the eyelid (which is inverted) andobserved from the inner surface. This generally requires two hands. Thefirst hand holds the light source in place on the outside of the eyelidwhile the second hand pulls the eyelid over the light source and bendsit into a position where the desired areas can be visualized using aslit lamp microscope or photographically imaged. The technique isdifficult to administer and due to its very nature will not allow thephysician to visualize the vessels and glands in their normal anatomicalstate due to the manipulation required to invert and bend the eyelidover the light source. Use of any of the devices such as depicted inFIG. 30, or 32-25 or 37, the disclosed device solves the “ease of use”problem and will allow the glands to be visualized in their nearlynormal anatomical state. The physician's hands are free to adjust theslit lamp magnification and/or perform any desired lid manipulation.Additionally, the light source illuminates the entire upper and lowereyelid simultaneously.

Since the light source is placed on the back of the eyelid and aimedoutward, the chance of accidental exposure of the eye to any harmfullight source is minimized. The light source can be tuned to differentfrequencies which would more readily be transmitted or absorbed into thetissue. The light source can also be tuned to provide some heating tothe eyelid as well as providing the trans-illumination function. Byproviding such heating, the therapeutic effects of the device can becarried out while simultaneously providing the ability to observe theMGs. Moreover, if the heating is appropriately tuned, to provide enoughheating power, a single lenspiece could be used to replace the heatedlenspiece portion of the device depicted in the provisional application.The particular light source being used can be tuned to balance theamount of light provided by adjustment of absorption and penetrationproperties of the device to strike a desired balance between providingillumination and providing heating.

Research has been conducted on photothermolysis where it has been shownthat certain light wavelengths absorb more in lipid rich material. Thisimplies that selection a wavelength could allow the illuminatedlenspiece to provide a level of heating to lipid-rich meibomian glandswhile providing a reduced level of heat to the surrounding tissue. Thiswould in turn cause the glands to appear darker while trans-illuminatingthereby visually tagging lipid rich areas and thus facilitatingvisualization. Additional research and experimentation can be conductedto verify this benefit in MGD treatment and visualization, however, itis noted that U.S. Pat. No. 7,060,061 to Altshuler et al. indicates thatlipid rich material has a preferential absorption wavelength of light.

In the exemplary embodiments depicted, the light source depicted can beembodied as an array of Light Emitting Diodes (LEDs) components mountedon a flexible circuit or a series of light pipes. By illuminating theeyelid from the inside surface the physician will be able to use hisstandard slit lamp microscope to visualize the Tran illuminated tissuewithout manipulating the eyelid.

By replacing the heater assembly shown in the provisional applicationwith a series of LEDs the lenspiece serves as a light source. Thelenspiece, once placed on the eye, will illuminate the eyelid. Thephysician, technician, etc. can visualize the light as it passes throughthe eyelid by use of a slit lamp microscope or can capture images asdescribed above using a suitable camera arrangement. The resulting imagewill show darker areas where light is absorbed more than other areas.The present device therefore provides a hands free method and allowingthe physician to view the glands while they are oriented in their normalanatomical position.

Certain wavelengths of light, as noted above, appear to be morepreferentially absorbed by lipid rich material. The field of selectivephotothermolysis has performed studies in this area that indicate thatthe wavelengths of 880 nm to 935 nm; 1160 nm to 1230 nm; 1690 nm to 1780nm; and 2250 nm to 2450 nm may have higher absorption in lipid than thesurrounding tissue. Hence, use of light in these wavelengths wouldlikely assist in providing a visual tag on the lipids by making the areaof lipid rich material appear darker than the tissue areas surroundingit. Alternatively, it appears likely that there are particularwavelengths of light that is more likely to preferentially pass lightthrough lipid rich material while preferentially being absorbed in thesurrounding tissue. A wavelength with that particular characteristicwould show the glands a being lighter than the surrounding tissue.Again, experimentation with various light sources can be done toidentify a light wavelength range that provides enhancement of contrastbetween the MGs and surrounding. Additionally, such contrast may beenhanced by using a broader spectrum of light and filtering the light toenhance the contrast.

If a light wavelength is selected which absorbs into tissue then heatingwill result. Infra red wavelengths have such properties and would be analternative to a resistively heated lenspiece. The infrared lightpenetrates the eyelid and heat will be generated as it is passesthrough. A temperature sensor placed at or near the inner eyelid andanother sensor placed at or near the outer eyelid can be used toregulate the temperature in much the same manner as that disclosed inthe above-referenced provisional application. The portion of electricalenergy which does not convert to light will be translated into heat muchthe same as the existing heating element. Therefore, not only will theLED assembly provide a penetrating heat source, it will also provide acontact heat source with the added benefit of illuminating the eyelids.

The illumination effect will enable the ophthalmologist, optometrist,technician, etc., to view the vessels and glands within the eyelid underthe magnification of their slit lamp microscopes. The trans-illuminationprocess will potentially enable visualization of the glands before useof the device depicted in the provisional application procedure or othertherapeutic procedure and after the procedure without needed anyadditional specialized equipment. The LED lenspiece is simply placedonto the patients eye, then the lenspiece is provided with power and asimple slit lamp microscopic examination of the eyelid will provide a“before” look at the eyelid vessels and glands. The eyecup portion isthen attached to the device depicted in the provisional application andperforms the procedure using the illuminated lens to provide thetherapeutic heat. Once finished they simply remove the eyecup whileleaving the lens in place and use the trans-illumination effect of thelens to perform an “after” examination of the eyelid vessels and glands.

Thus, in one embodiment consistent with the present invention, a methodof imaging a mammalian meibomian gland or other section of an eyelidinvolves shining a light on the outer surface of the eyelid in order totrans-illuminate a portion of the eyelid with oblique illumination; andfrom the outer surface of the eyelid, capturing an image oftrans-illuminated portion of the eyelid.

In certain embodiments, the captured image is stored in an electronicstorage medium and/or displayed on a video display. In certainembodiments, the shining and capturing are repeated at an adjacentlocation of the outer surface of the eyelid. In certain embodiments, theimages from the first and adjacent locations are combined. In certainembodiments, the combining includes stitching, adding, or averaging theimages from the first and adjacent locations to produce a resultantimage of a larger area of the eyelid. In certain embodiments, the lightincludes infrared light radiation and capturing the image is carried outusing infrared photography. In certain embodiments, the light includesvisible light radiation and capturing the image is carried out usingvisible light photography. In certain embodiments, a computer readablestorage medium can store instructions which, when executed on aprogrammed processor, carry out these methods.

In another embodiment, a method of imaging a mammalian patient'smeibomian gland or other section of an eyelid of an eye involves placinga contact lens in contact with the eye; having the patient close theeye; illuminating the contact lens to generate light emitting from thelens through the eyelid from the posterior surface of the eyelid; andfrom the outer surface of the eyelid, capturing an image of atrans-illuminated portion of the eyelid. In certain embodiments, thecaptured image is stored in an electronic storage medium and/ordisplayed on a video display or otherwise rendered. In certainembodiments, the method further involves repeating the illumination andcapturing of an image at a second location on the eyelid, and processingthe images to produce a single composite image. In certain embodiments,the light includes infrared light radiation and capturing the image iscarried out using infrared photography. In certain embodiments, thelight includes visible light radiation and capturing the image iscarried out using visible light photography. In certain embodiments, acomputer readable storage medium can store instructions which, whenexecuted on a programmed processor, carry out these methods.

In another embodiment, a method of imaging a mammalian meibomian glandor other section of an eyelid involves placing a light source at a firstposition adjacent an outer surface of the eyelid in order totrans-illuminate a portion of the eyelid from an outer surface thereof;from the outer surface of the eyelid, capturing a first image oftrans-illuminated portion of the eyelid, the first image containing atleast a portion of the light source; repositioning the light source to asecond position adjacent an outer surface of the eyelid in order totrans-illuminate a portion of the eyelid from an outer surface thereof;from the outer surface of the eyelid, capturing a second image oftrans-illuminated portion of the eyelid, the second image containing atleast a portion of the light source; and computing a composite of thefirst and second image to produce a resulting image.

In certain embodiments, a computer readable storage medium can storeinstructions which, when executed on a programmed processor, carry outthese methods. In certain embodiments, the computing of the compositeimage is carried out by a process of averaging, stitching or adding thefirst and second images. In certain embodiments, a composite image iscomputed by subtracting a light source obstruction from the image. Incertain embodiments, the resulting image is stored in an electronicstorage medium and/or displayed on a video display or otherwiserendered. In certain embodiments, the light source includes an infraredlight radiation source and capturing the images is carried out usinginfrared photography. In certain embodiments, the light source includesa visible light radiation source and capturing the images is carried outusing visible light photography.

In another embodiment consistent with the present invention an apparatusfor imaging a portion of a mammalian eyelid has a light source suitablefor directing light to a portion of the outer surface of the eyelidusing oblique illumination in order to trans-illuminate the portion ofthe eyelid. An optical receiver is provided that is suitable forreceiving light transmitted through a portion of the eyelid andproducing an output signal related to characteristics of thetrans-illuminated portion of the eyelid, the light receiver receivinglight from the outer surface of the eyelid. An image processor receivesthe output signal and captures an image from the light receiver.

In certain embodiments, an electronic storage device stores the capturedimage. In certain embodiments, a display displays the captured image. Incertain embodiments, the light source directs light to the portion ofthe outer surface of the eyelid via a first optical fiber. In certainembodiments, the optical receiver receives light from the outer surfaceof the eyelid via a second optical fiber. In certain embodiments, thelight source directs light to the portion of the outer surface of theeyelid via a first optical fiber, and the optical receiver receiveslight from the outer surface of the eyelid via a second optical fiber,and the first and second optical fibers are positioned in a fixedgeometric relationship with one another. In certain embodiments, thefirst and second optical fibers are positioned to direct light at aspecified angle and receive the light at the specified angle as measuredfrom a plane approximation of the surface of the eyelid. In certainembodiments, the first and second optical fibers are commonly containedin a single handpiece that holds the first and second optical fibers inthe fixed geometric relationship with one another. In certainembodiments, multiple adjacent locations of the outer surface of theeyelid are imaged. In certain embodiments, a processor combines theimages from the multiple adjacent locations. In certain embodiments, aprocessor stitches the images from the multiple adjacent locations toproduce a resultant image of a larger area of the eyelid. In certainembodiments, a processor sums the images from the multiple adjacentlocations. In certain embodiments, the light source comprises aninfrared light source and wherein the optical receiver is compatiblewith infrared light. In certain embodiments, the light source comprisesa visible light source and wherein the optical receiver is compatiblewith visible light.

In another embodiment, an apparatus for imaging a portion of a mammalianeyelid has a light source. A contact lens is configured to receive lightfrom the light source and direct the light through an eyelid fromposterior to anterior surface to thereby trans-illuminate the eyelid,when the light source illuminates the contact lens, a camera records animage of the eyelid as it is trans-illuminated. In certain embodiments,an image processor, receives an output signal from the camera andprocesses the output signal to enhance the image. In certainembodiments, an electronic storage device stores the captured image. Incertain embodiments, a display displays the captured image. In certainembodiments, the light source includes an infrared light source andwherein the camera is compatible with infrared light. In certainembodiments, the light source includes a visible light source andwherein the camera is compatible with visible light.

In another embodiment, an apparatus for imaging a portion of a mammalianeyelid has a light source configured to direct light through an eyelidfrom an anterior surface to thereby trans-illuminate the eyelid. Acamera records an image of the eyelid as it is trans-illuminated. Apositioning mechanism automatically positions the light source at aplurality of locations adjacent the eyelid and record a plurality ofimages at each of said plurality of locations using the camera. Aprocessor averages the plurality of images to produce a resultant image.

In certain embodiments, an electronic storage device stores theresultant image. In certain embodiments, a display displays theresultant image. In certain embodiments, the light source comprises aninfrared light source and wherein the camera is compatible with infraredlight. In certain embodiments, the light source includes a visible lightsource and wherein the camera is compatible with visible light.

FIG. 38 depicts an exemplary comprehensive imaging and treatment process900 that can be used for diagnosis and treatment of MGD using any of theimaging techniques disclosed herein starting at 904. At 906, the eyelidis imaged without any application of force to the eyelid itself. Process906 may not be possible since the contact with the eyelid by the imagingdevice may meet or exceed the pressure of blinking. At 908, pressure isapplied to the eyelid and the eyelid is re-imaged at 914 while thepressure is present. Once the imaging is completed, a diagnosis can bemade and an appropriate course of treatment can be carried out in aneffort to resolve the condition observed. The effectiveness of thetreatment can then be evaluated by re-imaging the eyelid at 920 withoutpressure, as well as applying pressure at 924 and re-imaging the eyelidunder pressure at 930. A determination can then be quantitatively madeat 934 as to the effectiveness of the treatment and either the processcan end at 938 or further diagnosis and treatment carried out at 916. Itis noted that for ultrasound imaging, processes 908 and 920 may not bepossible since the contact with the eyelid may meet or exceed thepressure of blinking. However, the application of pressure in thisapplication may permit imaging of the MG while in the act of secretingwhen the gland is at least partially properly functioning and not fullyoccluded. Many variations are possible including only imaging with orwithout pressure applied to the eyelid at any stage according to thepreferences of the physician, experiences with the patient, imagingtechnique used or other factors.

In order to use any of the above embodiments of imaging techniques andapparatus, it is possible (likely in many instances) that the patientwill be more comfortable and thus the imaging process can proceed easierif a topical anesthetic is applied to the outer surfaces of the eyes andto the eyelids. This facilitates greater comfort when the images arecreated and while the eyelids are manipulated where such manipulation isneeded. Moreover, such anesthetic may be beneficial in minimizingpatient blinking.

Those skilled in the art will appreciate, upon consideration of thepresent teachings, that any of the above techniques described can beused to provide reference, pre-treatment and post treatment images ofone or more meibomian glands or the eyelid so as to provide diagnosisand records of treatment success.

Those skilled in the art will recognize, upon consideration of the aboveteachings, that certain of the above exemplary embodiments are basedupon use of a programmed processor. However, the invention is notlimited to such exemplary embodiments, since other embodiments could beimplemented using hardware component equivalents such as special purposehardware and/or dedicated processors. Similarly, general purposecomputers, microprocessor based computers, micro-controllers, opticalcomputers, analog computers, dedicated processors, application specificcircuits and/or dedicated hard wired logic may be used to constructalternative equivalent embodiments.

Certain embodiments described herein, are or may be implemented using aprogrammed processor of any suitable design including general purpose,RISC, special purpose and other programmable processor types executingprogramming instructions that are broadly described above in flow chartform that can be stored on any suitable electronic or computer readablestorage medium and/or can be transmitted over any suitable electroniccommunication medium. However, those skilled in the art will appreciate,upon consideration of the present teaching, that the processes describedabove can be implemented in any number of variations and in manysuitable programming languages without departing from embodiments of thepresent invention. For example, the order of certain operations carriedout can often be varied, additional operations can be added oroperations can be deleted without departing from certain embodiments ofthe invention. Error trapping can be added and/or enhanced andvariations can be made in user interface and information presentationwithout departing from certain embodiments of the present invention.Such variations are contemplated and considered equivalent.

Software and/or firmware embodiments may be implemented using aprogrammed processor executing programming instructions that in certaininstances are broadly described above in flow chart form that can bestored on any suitable electronic or computer readable storage medium(such as, for example, disc storage, Read Only Memory (ROM) devices,Random Access Memory (RAM) devices, network memory devices, opticalstorage elements, magnetic storage elements, magneto-optical storageelements, flash memory, core memory and/or other equivalent volatile andnon-volatile storage technologies) and/or can be transmitted over anysuitable electronic communication medium. However, those skilled in theart will appreciate, upon consideration of the present teaching, thatthe processes described above can be implemented in any number ofvariations and in many suitable programming languages without departingfrom embodiments of the present invention. For example, the order ofcertain operations carried out can often be varied, additionaloperations can be added or operations can be deleted without departingfrom certain embodiments of the invention. Error trapping can be addedand/or enhanced and variations can be made in user interface andinformation presentation without departing from certain embodiments ofthe present invention. Such variations are contemplated and consideredequivalent.

Ranges provided, for magnification and light wavelengths for example,are to be interpreted to include all possible sub-ranges within thedisclosed ranges.

While certain illustrative embodiments have been described, it isevident that many alternatives, modifications, permutations andvariations will become apparent to those skilled in the art in light ofthe foregoing description.

1. An apparatus for facilitating trans-illumination of an eyelidcovering an eye, comprising: an eye shield having curvature that isconfigured to approximately match a portion of a curvature of anexternal surface sclera of the eye, the eye shield having an innersurface that contacts the eye and an outer surface; the eye shieldhaving properties that render the eye shield opaque to light of aparticular spectrum; and an array of light sources disposed on the outersurface that produce light in the particular spectrum in order totrans-illuminate the eyelid from a posterior side of the eyelid.
 2. Theapparatus according to claim 1, wherein the array of light sourcescomprises an array of light emitting diodes (LEDs).
 3. The apparatusaccording to claim 2, wherein the array of LEDs comprise surface mountLEDs.
 4. The apparatus according to claim 2, further comprising aflexible circuit board affixed to the outer surface and wherein the LEDsin the array of LEDs are attached to the flexible circuit board.
 5. Theapparatus according to claim 4, further comprising an outer mold thatcovers the array of LEDs in a manner that produces a smooth surface. 6.The apparatus according to claim 4, wherein the flexible circuit boardis reflective of light of the particular spectrum.
 7. The apparatusaccording to claim 1, further comprising an outer mold that covers thearray of light sources in a manner that produces a smooth surface. 8.The apparatus according to claim 7, wherein the outer mold has lightfiltering or diffusing properties.
 9. The apparatus according to claim7, wherein the outer mold is transparent to the light of the particularspectrum.
 10. The apparatus according to claim 1, further comprising anelectrical connector that provides electrical current to the array oflight sources.
 11. The apparatus according to claim 1, furthercomprising means for supplying electrical current to the array of lightsources.
 12. The apparatus according to claim 1, wherein the outersurface is reflective of light of the particular spectrum.
 13. Anapparatus for facilitating trans-illumination of an eyelid covering aneye, comprising: an eye shield having curvature that is configured toapproximately match a portion of a curvature of an external surfacesclera of the eye, the eye shield having an inner surface that contactsthe eye and an outer surface; the eye shield having properties thatrender the eye shield opaque to light of a particular spectrum; aflexible circuit board affixed to the outer surface; an array of surfacemount light emitting diodes (LEDs) disposed on the flexible circuitboard that produce light in the particular spectrum in order totrans-illuminate the eyelid from a posterior side of the eyelid; anouter mold that covers the array of surface mount LEDs in a manner thatproduces a smooth surface; and means for supplying electrical current tothe array of surface mount LEDs.
 14. The apparatus according to claim13, wherein the flexible circuit board is reflective of light of theparticular spectrum.
 15. The apparatus according to claim 13, whereinthe outer mold has light filtering or diffusing properties.
 16. Theapparatus according to claim 13, wherein the outer mold is transparentto the light of the particular spectrum.
 17. The apparatus according toclaim 13, wherein the outer surface is reflective of light of theparticular spectrum.
 18. An apparatus for facilitatingtrans-illumination of an eyelid covering an eye, comprising: anelongated handle having an end; an eye shield affixed to the end of theelongated handle, the eye shield having opposing lighting and shieldingsurfaces; the eye shield having properties that render the eye shieldopaque to light of a particular spectrum; an array of light sourcesdisposed on the lighting surface that produce light in the particularspectrum in order to trans-illuminate the eyelid from a posterior sideof the eyelid when the eye shield is placed between the eyelid and theeye, and simultaneously shields the eye from direct light emanating fromthe array of light sources; and wherein the eye shield and the array oflight sources are flat enough to fit between the eyelid and the eye. 19.The apparatus according to claim 18, wherein the array of light sourcescomprises an array of light emitting diodes (LEDs).
 20. The apparatusaccording to claim 19, wherein the array of LEDs comprise surface mountLEDs.
 21. The apparatus according to claim 19, further comprising aflexible circuit board affixed to the lighting surface and wherein theLEDs in the array of LEDs are attached to the flexible circuit board.22. The apparatus according to claim 21, further comprising an outermold that covers the array of LEDs in a manner that produces a smoothsurface.
 23. The apparatus according to claim 21, wherein the flexiblecircuit board is reflective of light of the particular spectrum.
 24. Theapparatus according to claim 18, further comprising an outer mold thatcovers the array of light sources in a manner that produces a smoothsurface.
 25. The apparatus according to claim 24, wherein the outer moldhas light filtering or diffusing properties.
 26. The apparatus accordingto claim 24, wherein the outer mold is transparent to the light of theparticular spectrum.
 27. The apparatus according to claim 18, whereinthe elongated handle includes a source of electrical current thatsupplies electrical current to the array of light sources.
 28. Theapparatus according to claim 18, further comprising means for supplyingelectrical current to the array of light sources.
 29. The apparatusaccording to claim 18, wherein the lighting surface is reflective oflight of the particular spectrum.